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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2010  |  Volume : 21  |  Issue : 2  |  Page : 222-231
Paraneoplastic syndromes and the kidney

Division of Nephrology, Department of Internal Medicine, Walter Cantidio University Hospital, Medicine School, Federal University of Ceara, Brazil

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Date of Web Publication9-Mar-2010


A paraneoplastic syndrome is defined as a group of symptoms that develop when substances released by some cancer cells disrupt the normal function of the surrounding cells and tissue. Paraneoplastic renal syndromes are diseases that indirectly compromise tubular and glomerular function by electrolyte imbalance, hormone-producing tumors or deposition of antigen-antibody complexes in the glomeruli. In order to describe the most common paraneoplastic syndromes, which may compromise the renal function, an extensive review was performed of papers, including case reports, guidelines, meta-analysis and other scientific publications. Renal function can be affected by many paraneoplactic syndromes: hypercalcemia in malignancies, syndrome of inappropriate sec­retion of antidiuretic hormone, tumor lysis syndrome, renin-producing tumors and paraneoplastic glomerulopathies. An early diagnosis and effective treatment might improve quality of life and alter prognosis of these patients.

How to cite this article:
de Oliveira Filgueira P, Vasconcelos LF, da Silva GB, Daher EF. Paraneoplastic syndromes and the kidney. Saudi J Kidney Dis Transpl 2010;21:222-31

How to cite this URL:
de Oliveira Filgueira P, Vasconcelos LF, da Silva GB, Daher EF. Paraneoplastic syndromes and the kidney. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2022 Sep 29];21:222-31. Available from: https://www.sjkdt.org/text.asp?2010/21/2/222/60057

   Introduction Top

Auche described, in 1890, the first report of a paraneoplastic syndrome with involvement of the peripheral nervous system in patients with cancer. [1] However, the word "paraneoplastic" was first used only in 1949 by Guichard and Vignon, when they discussed the differential diagnosis of a patient with central and periphe­ral neuropathies caused by metastasis of a cer­vical neoplasia. [2] Guichard et al, found on nec­ropsy studies in patients with equal neuropa­thies, that there were no neoplastic cells in the spinal cord of these patients. As discovered, the authors decided using the term paraneoplastic, and not neoplastic, to describe these polyneu­ropathies. [3] Nowadays, the expression "paraneo­plastic syndrome" is defined as a group of symp­toms that may develop when substances relea­sed by some cancer cells disrupt the normal function of surrounding cells and tissue. [4]

A paraneoplastic syndrome should be suspec­ted in the presence of the following charac­teristics: absence of a defined etiology for the associated syndrome; correlation between the time of diagnosis of the syndrome and that of the cancer; clinical and histological remission after complete surgical or chemotherapy treat­ment and worsening of the symptoms due to tu­mor residue. [5],[6]

Paraneoplastic syndromes are a group of di­seases, which indirectly compromise renal fun­ction by causing electrolyte imbalance, ectopic secretion of hormones or deposition of antigen­antibody complexes in the glomeruli, sometimes at the same time. Paraneoplastic renal syndromes are increasing in frequency among the older po­pulation. [7],[8]

The present article is the result of a systematic search at Pubmed database of papers, including case reports, guidelines, meta-analysis and other scientific publications using the terms "paraneo­plastic and renal and glomerulopathies", "para­neoplastic and renal and syndromes", "hypercal­cemia and malignancy", "innapropriate and sec­retion and antidiuretic and hormone", "tumor and lysis and syndrome" and "renin and producing and tumors".

   Paraneoplastic Syndromes Affecting Renal Function: Hypercalcemia of Malignancy Top

Hypercalcemia is one of the most common metabolic disorders in patients with advanced cancer. It is more frequent in adults and rarely seen in children. [9] Around 10 to 30% of patients with cancer present this complication, depen­ding on the primary tumor. [10] The histology of the tumor also predicts the risk of developing hypercalcemia. The incidence of this complica­tion may be decreasing due to early therapy with bisphosphonates, particularly in patients with multiple myeloma and breast cancer. As this complication may cause renal insufficiency, coma and death, it should be well known in order to institute an effective treatment. [11] Hy­percalcemia of malignancy is directly caused by an increase in calcium release from bone, dec­rease of calcium excretion from renal tubules and is classified as follows: [12]

Local osteolytic hypercalcemia (LOH): osteo­lytic metastases cause massive bone resorption, pain, bone fractures, spinal cord compression syndrome and hypercalcemia in advanced cases. Some factors produced by the tumor are respon­sible for osteoclastic activation and bone des­truction; they include linfotoxin, interleukin-1 (IL-1), interleukin-6 (IL-6), parathormone-rela­ted peptide (PTHrP), hepatocyte growth factor (HGF), macrophage inflammatory protein (MIP­1alfa) and receptor activator of nuclear factor­kappa B ligand (RANKL). [13] Malignancies that commonly cause bone metastases are solid tumors including breast, prostate, lung and he­matological malignancies, as well as multiple myeloma and lymphomas. [14]

Malignant humoral hypercalcemia (MHH): This is a syndrome wherein the tumor produces cal­cium stimulating factors, principally PTHrP. It is the cause of hypercalcemia in 80% of pa­tients with malignancies. [15] Increased levels of PTHrP will act on the PTH-1 receptor in the bone and kidney causing diffuse bone resorp­tion, phosphaturia (hypophosphatemia) and also an increase in tubular calcium reabsorption. In a different way from PTH, the PTHrP does not stimulate the production of 1,25 dihydroxyvita­min D. [16] Tumors frequently involved with this condition include squamous cells carcinomas, kidney, ovarian, endometrial and breast carci­nomas and HTLV-1-associated lymphomas.

Ectopic hyperparathyroidism: This is characte­rized by PTH production by non-parathyroid tumors. These rare cases have been described in ovarian, lung, thyroid and neuroendocrine tumors, leukemias and thymomas. We must always re­member that primary hyperparathyroidism may occur without being related to the primary tu­mor. [17]

Active vitamin D (1,25 dihydroxyvitamin D) pro­duced by the tumor: This increases intestinal absorption of calcium. Lymphomas are the most commonly involved tumors. [18]

Generally, renal and neurologic complications are proportional to the degree of hypercalcemia, which is considered mild when total calcium level is between 10.5 and 11.9 mg/dL, moderate when between 12 and 13.9 mg/dL and severe when higher than 14 mg/dL. In the presence of hypoalbuminemia, total calcium levels might be falsely low, and so, correction of total calcium levels must be made as follows: corrected total calcium = measured total calcium + 0.8 × (4 - albumin). [12] Most hypercalcemic patients pre­sent with nonspecific symptoms such as fatigue (70%), anorexia (60%), constipation (60%), weight loss (60%), bone pain (60%), polyuria, polydipsia and dehydration. [19]

The most common renal alterations due to hy­percalcemia in malignancies are nephrogenic dia­betes insipidus and acute or chronic renal insuf­ficiency, which may lead to an oncologic emer­gency. Hypercalcemia-related polyuria occurs because of renal incapacity to concentrate urine, caused directly by the increase of serum cal­cium, which limits vasopressin (ADH) action in renal collecting ducts. It was experimentally de­monstrated that, when calcium concentration ri­ses in the lumen of renal tubules, calcium/poly­cation apical receptors localized at cell mem­branes of the terminal portion of the collecting duct in renal medulla decrease the ADH-me­diated osmotic response. [20]

Hypercalcemia due to bone involvement may also cause increase in serum phosphorus, which can cause complications such as nephrocalcino­sis and interstitial nephritis. Hypercalciuria and nephrolithiasis can also occur. Gastrointestinal symptoms (anorexia, nausea and vomiting) as­sociated with the renal disorders further con­tribute to patient's dehydration. Dehydration re­sults in decrease of the glomerular filtration rate and lower calcium excretion. Polyuria also in­creases potassium, magnesium and phosphorus excretion causing weakness and hypotonia. [21]

In order to initiate a specific therapy for the primary neoplasia, it is essential to institute treat­ment of hypercalcemia, to achieve better clini­cal response. [Table 1] shows important measures to treat hypercalcemia of malignancy. [22]

   Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) Top

The ADH, or vasopressin, is a ring-shaped pep­tide with a molecular weight of 1228 KDa. [23] It is produced as a pre-pro-hormone, which is me­tabolized into a pro-hormone at the paraventri­cular and supraoptic nucleus of the hypotha­lamus and then transported to the hypophysis, where the final precursor is activated. [24]

The main regulator of vasopressin secretion is the osmotic pressure. When it rises, more vaso­pressin is released and more water is absorbed. On the contrary, vasopressin levels decrease in association with water absorption and dilute urine. Other mechanisms, such as the blood pre­ssure and the nasopharyngeal reflex, participate in control of vasopressin secretion. [25],[26]

Vasopressin causes water absorption at the co­llecting ducts of the nephron. When it interacts with its type-2 receptors, ADH activates a phos­phorylation cascade, which results in transloca­tion of aquaporin water channels, a water transporting protein, causing water passage from the nephron's lumen to the renal interstitium. [27] Cri­teria for SIADH includes a sodium serum level lower than 135 mEq/L, blood osmolality lower than 280 mOsmol/kg due to extracellular vo­lume expansion, rise in plasma volume, urine hypertonicity (compared with blood) and ab­ sence of dehydration. [28],[29],[30]

Malignant neoplasias represent the main cause of SIADH and are related to the release of an active ADH or its pro-hormone. Examples of neoplasias which are associated with SIADH include: small cell lung carcinomas (reaching 15% of cases), [31],[32] head and neck cancers and also carcinomas of the breast, pancreas, sto­mach, ureter, prostate, bladder and duodenum. There are reports of cases of SIADH in lym­phomas, leukemias, thymomas, thymic neuro­blastoma, olphactory neuroblastoma, Ewing's sarcoma, mesothelioma, immature ovarian tera­toma and melanoma. [31],[33]

Clinically, the presentation is extremely varia­ble and depends mainly on the degree of hy­ponatremia and how fast the disease progresses. Generally, the speed of reduction of serum so­dium level is more related to serious neurologic injury than the sodium level itself. When so­dium level is between 125 and 135 mEq/L, pa­tients are, most of the time, asymptomatic; when it is around 125 mEq/L, nausea, vomiting, ano­rexia, weakness and mental alterations may emerge; when below 120 mEq/L, coma and death are possible. [29],[34],[35] Signs that may suggest hyponatremia are pseudobulbar paralysis, posi­tive Babinski sign and extrapyramidal signs. [36] When there is previous brain injury, these signs may occur with higher sodium levels. Hypona­tremic encephalopathy (mental confusion and dis­orientation) is rare and occurs in 7% of cases. [30],[37] Patients with SIADH are hypervolemic, although they normally do not develop edema.

For proper diagnosis of SIADH it is necessary to confirm that thyroid, adrenal and renal func­tions are normal and that no diuretic is being administered. [31],[38],[39] The definitive diagnosis of an ADH-secreting tumor is only made by his­topathologic studies and indirect immunofluo­rescence of tumor cells.

Treatment consists of surgical removal of the ectopic source of ADH and/or radiotherapy and/ or chemotherapy depending on the tumor cha­racteristics. In some cases, reduction of water ingestion and sodium replacement are necessary. Future alternatives for treatment include super­selective antagonists of V2 ADH-receptors.

   Tumor lysis Syndrome Top

Tumor lysis syndrome is an oncologic emer­gency caused by destruction of neoplastic cells, either spontaneously, or more frequently, secon­dary to chemotherapy or radiotherapy of the malignant tumors. [40]

During the lysis process, many intracellular compounds are released into the extracellular matrix due to the loss of the cellular membrane. It occurs mostly secondary to chemotherapy or radiotherapy of hematologic malignancies such as Burkitt's lymphoma, acute lymphoblastic leu­kemia and high grade non-Hodgkin's lympho­mas. [41] Tumor lysis syndrome is a serious side effect of chemotherapy (massive tumor cells destruction) and can also occur spontaneously, in the absence of any cytotoxic treatment.

When the syndrome occurs, uric acid, phos­phate and potassium are the most important com­pounds released from the intracellular compart­ment. [41] Due to the enormous quantity of these compounds released into the blood, there is re­nal overfunction and life-threatening risks. Signs and symptoms usually begin between one to five days after cytotoxic therapy. Uric acid, the most important compound related to the clinical manifestations of the syndrome, is synthesized from nucleic acid metabolism. It has low uri­nary solubility and may precipitate in the co­llecting ducts of the renal tubular system when there are high concentrations of uric acid and low urinary pH. Patients have hyperuricemia when serum level of uric acid is above 8 mg/dL. When serum level is between 10 and 15 mg/dL, patients may present nonspecific symp­toms such as lethargy, nausea and vomiting. The most feared consequence of the tumor lysis syndrome is an acute oliguric renal insufficiency due to deposition of uric acid crystals in the renal tubules. This complication usually occurs when serum acid uric is above 20 mg/dL. We can differentiate the tumor lysis syndrome cau­sing acute renal insufficiency from other types of acute renal insufficiencies by noting that the ratio of urinary uric acid and creatinine is above one.

Potassium levels may rise quickly in the pre­sence of the syndrome and can be life-threate­ning. High levels of potassium may cause nau­sea, vomiting, weakness and cardiac arrhyth­mias. It is very important to look out for alte­rations in serum potassium levels when tumor lysis syndrome is suspected. [42]

Hyperphosphatemia is also a consequence of the syndrome and is usually associated with hy­percalcemia. When the product calcium/phos­phorus is above 55, calcium phosphate precipi­tation and deposition in the tissues may occur, including in the renal tubules causing loss of function. [41],[43]

Prevention of tumor lysis syndrome is more effective than the treatment itself and must be routinely made in the first 24 to 48 hours before chemotherapy for aggressive hematological ma­lignancies. [44],[45] It consists on vigorous hydra­tion which causes high glomerular filtration rate and promotes excretion of the metabolites of the tumor lysis syndrome. It is recommended to use 3 liters of saline solution per m² of body surface area. [45] The use of allopurinol, an inhi­bitor of the xantine oxidase enzyme which acts on the synthesis of the uric acid, is also recom­mended. Urinary alkalinization with sodium bi­carbonate is important because uric acid preci­pitation is rare with high pH. Chemotherapy is only indicated for patients with high-risk for tumor lysis syndrome, if the serum uric acid is below 8 mg/dL and creatinine lower than 1.6 mg/dL. [45] If these general measures are not su­fficient, the use of the recombinant enzyme urate oxidase is capable of metabolizing uric acid into alantoine, a soluble compound.

During the syndrome, the same preventive mea­sures must be undertaken, although urine alka­linization is not done due to the risk of calcium phosphate precipitation in the kidneys. Due to the risk of hyperkalemia, all patients with se­rum potassium higher than 6 mEq/L must be monitored through electrocardiogram. If cardiac alterations are detected, hypokalemic measures must be undertaken using calcium gluconate, glucose and ion-exchange resins. [45]

High phosphate levels can be managed with massive hydration, but in refractory cases, phos­phate binders such as calcium carbonate and sevelamer should be used. Despite all thera­peutic measures, patients with tumor lysis syn­drome may present with severe electrolyte and metabolic diseases and might require dialysis. [45]

   Renin-producing Tumors Top

The renin-angiotensin-aldosterone system is responsible for the correct control of blood pre­ssure as well as electrolyte balance. Renin is produced mainly in the kidneys, even though it is also found in the brain, genital tract, salivary glands, blood vessels and skeletal muscles, in­cluding the heart. [46]

Renin-producing tumors are rare entities, which are poorly reported and cause secondary hyper­tension in patients who present high levels of plasma renin activity (PRA) and plasma aldos­terone concentration (PAC). Its proper diagno­sis may offer a good opportunity to correct electrolyte imbalance and hypertension. [47]

These tumors can be classified into reninomas (tumors arising from the juxtaglomerular appa­ratus of the kidneys), other renal tumors sec­reting renin and extrarenal renin-producing tu­mors. All of them are uncommon causes of se­condary hyperaldosteronism. Research involving 75 cases of renin-producing tumors showed that 36 cases (48%) were juxtaglomerular cell tu­mors, 21 (28%) were extrarenal renin-producing tumors and 18 (24%) were other renal tumors secreting rennin. [48] The rare extra-renal tumors that may produce renin include ovarian, lung, pancreas, adrenal and colonic cancers. [46]

Clinically, renin-producing tumors are charac­terized by a triad of hypertension, hypokalemia and elevated PRA. [46] A review study showed that 89 patients with reninomas presented a mean systolic blood pressure of 201 mmHg and a mean diastolic blood pressure of 130 mmHg. [47] In the same research, hypokalemia was detected, at the time of the diagnosis, in 81% of cases. [47] Other common symptoms include head-ache, nausea, polyuria, nycturia, polydipsia and fatigue. The presence of a renin-producing tumor is strongly suspected when high levels of pro-renin are found, an inactive renin precursor. [49] A plasma concentration of pro-renin equal to, or above 1000 ng/mL is a strong evidence of a renin­ producing tumor .[50]

Renin-producing tumors alter the renal func­tion as they cause secondary hyperaldostero­nism and, as a consequence, produce severe hy­pokalemia (< 2.0 mEq/L) due to an increase of potassium excretion and chronic renal damage due to high blood pressure levels. Mild alkalo­sis can also be found, due to the high levels of aldosterone, which is responsible for hydrogen secretion coupled to sodium reabsorption by intercalated cells at the cortical renal tubule. [51],[52] In patients with reninomas, proteinuria and renal insufficiency have been described, respectively, in 11% and 3% of the cases. [47]

In juxtaglomerular cell tumors and in other re­nal tumors secreting renin, the definitive treat­ment is surgery, including total or partial neph­rectomy depending on the tumor site and, is associated with excellent results. [47] Treatment of the extrarenal renin-producing tumors may also be surgical, although they have worse progno­sis, except in low PRA cases which demons­trate a better survival. [46] Drugs that inhibit the renin-angiotensin system, such as angiotensin­converting enzyme inhibitors or angiotensin II receptor blockers, can be effectively adminis­tered for blood pressure control. Sometimes, the excessive renin secretion can block the effects of these antihypertensive agents. [53]

   Paraneoplastic Glomerulopathies Top

Included in the paraneoplastic syndromes, the concept of the paraneoplastic glomerulopathy was described by Galloway in 1922, when a case of nephrotic syndrome secondary to a Ho­dgkin's lymphoma was reported. [54] A vast num­ber of benign and malignant tumors are asso­ciated with glomerulonephritis. Neoplasias that commonly cause paraneoplastic glomerular di­seases are gastrointestinal and lung carcino­mas. [55] The real incidence of glomerulonephritis secondary to malignancies is not known be­cause many patients with cancer have urinary disorders. [56] Research involving 155 patients with membranous nephropathy (MN) showed that the cancer prevalence was related to age: 10% of patients above 60 years had a malignancy against only 1% of patients under 60 years. [57]

The most common glomerulopathy associated to solid tumors is MN, which generally presents as the nephrotic syndrome, characterized by pro­teinuria (> 3.5 g/24h/1.73m²), hypoalbuminemia, edema and hyperlipidemia. Cases of minimal change disease (MCD), IgA nephropathy (IgAN), focal and segmental glomerulosclerosis (FSGS), membranoproliferative glomerulonephritis (MP­GN), crescentic glomerulonephritis (RPGN), amy­loidosis and thrombotic microan-giopathy (T­MA) associated with tumors have been reported.

The pathophysiology is immune-mediated with the involvement of tumor-associated antigens and fetal and/or viral antigens. In some cases, the pathogenesis involves disseminated intra­vascular coagulation or amyloidosis. [58] In some patients, antigen deposits in renal glomeruli have been shown. [55]

   Membranous Nephropathy and Cancer Top

Many tumors have been described as a cause of MN with gastric and bronchogenic carcino­mas being most commonly involved, [59] although prostate and renal cell carcinomas and thymo­mas have a higher incidence than other solid tu­mors. So far, MN associated with hematological malignancies has been described in only 23 ca­ses, [60] including non-Hodgkin's lymphoma as the most commonly associated. Three characteris­tics are associated with an increase in the risk of finding cancer in patients with MN: age, use of tobacco and the histopathological finding of more than eight inflammatory cells in one glo­merulus. [61] Renal insufficiency as the first clini­cal finding appears to be more frequent in pa­tients with MN associated with malignancies. [62] The pathological mechanism responsible for the paraneoplastic MN has not been completely elucidated, but we may infer that there is an intense immune reaction. There are reports of carcinoembrionic antigens, prostate-specific an­tigens, melanoma antigens and non-identified tumor antigens in glomeruli of patients with neoplasias, that synthesize these antigens and develop MN. [59] The glomerular lesion may be initiated with an increase in the deposition of immune complexes in the renal glomeruli. The site of formation of immune complexes can be the blood or the glomerulus through the depo­sition of tumor antigens and tumor anti-antigen antibodies. [59]

   Minimal Change Disease and Cancer Top

Though MCD is more frequently associated with Hodgkin's lymphoma, it is also reported in association with non-hematological tumors, being more frequent in renal cell carcinoma and thy­moma. [59] So far, 94 cases of MCD have been described in association with hematological neo­plasias. [60]

   IgA Nephropathy and Cancer Top

There is a clear association between renal cell carcinoma and IgAN. Research involving 60 samples of nephrectomies performed for renal cell tumors, showed that 18% had IgAN, which is a very high prevalence for this type of glo­merulopathy. [63] Regression of proteinuria and hematuria was observed in six of 11 patients with IgAN after 2-3 months following neph­rectomy. [63] Other tumors that can be associated are esophagus and respiratory tract carcinomas. [59]

   Focal and Segmental Glomerulosclerosis and Cancer Top

Renal cell carcinomas and thymomas are the most commonly involved tumors. There are 15 cases in the literature of FSGS related to hema­tological neoplasias. [60] The glomerular toxicity associated to pamidronate can also cause FSGS. [59]

   Membranoproliferative Glomerulonephritis and Cancer Top

This glomerulopathy, when paraneoplastic, is more commonly associated with lymphoprolife­rative disorders and few cases associated with solid tumors have been described, including lung carcinoma, melanoma and renal cell car­cinoma. [59] Thirty-four cases of MPGN associa­ted with hematological neoplasias have been re­ported. [60]

   Crescentic Glomerulonephritis: Rapidly Progressive Glomerulonephritis and Cancer Top

RPGN related to cancer is rare in patients un­der 40 years old. [64] There is a high incidence of carcinomas associated with RPGN, predomi­nantly renal cell carcinomas, particularly in pa­tients with ANCA-positive primary vasculitis. [65]

   Thrombotic Microangiopathies (TMA) and Cancer Top

TMA cause thrombocytopenia, hemolytic ane­mia, ischemic manifestations (platelet aggluti­nation) and renal and central nervous system damage. In patients with cancer, the pathophy­siology is controversial: endothelial damage and the presence of protease inhibitors may con­tribute to its development. Most of the cases of TMA associated with cancer are described in patients with mucin-secreting carcinomas (gas­tric, lung and mammary), although it appears to be more frequent when there are already me­tastases. [66]

[Table 2] demonstrates all cases of paraneoplas­tic glomerulopathies reported in medical litera­ture secondary to non-hematologic tumors. [59]

   Conclusion Top

Different malignant tumors may alter renal function, through paraneoplastic syndromes. Even though paraneoplastic renal syndromes are rare, they are a major cause of morbidity and mor­tality among oncology patients. In some cases, depending on the primary neoplasia, the para­eoplastic glomerulopathy does not alter pa­tients' survival period and the prognosis is de­pendent on the primary tumor. On the other hand, even the treatment of the neoplasia can cause renal function damage, as in tumor lysis syndrome. An early diagnosis and effective treatment might improve quality of life and alter prognosis of these patients. Only with pro­per treatment of neoplasia, the associated para­neoplastic syndrome would remit.

   References Top

1.Cancereux. Rev Med 1890;10:785-807.  Back to cited text no. 1      
2.Guichard MM, Vignon G. The metastatic can-cerous polyradiculoneuropathy. Le J Medecine de Lyon 1949;197-207.  Back to cited text no. 2      
3.Guichard MM, Cabanne F, Tommasi M, Fayolle J. Polyneuropathies in cancer patients and para-neoplastic polyneuropathies. Lyon Medicale 1956; 41:309-29.  Back to cited text no. 3      
4.National Cancer Institute. Dictionary of Cancer Terms and Cancer related terms: Definition of Paraneoplastic syndrome (cited in 30/11/2008). Available from: http://www.cancer.gov/templa-tes/db_alpha.aspx?CdrID=46243 .  Back to cited text no. 4      
5.Ronco PM. Paraneoplastic glomerulopathies: New insights into an old entity. Kidney Int 1999;56(1): 355-77.  Back to cited text no. 5      
6.Davison AM. Renal diseases associated with malignancies. Nephrol Dial Transplant 2001;(16): 13-4.  Back to cited text no. 6      
7.Glassock RJ. Glomerular disease in the elderly population. Int Urol Nephrol 1998;8:149-54.  Back to cited text no. 7      
8.Cameron JS. Nephrotic syndrome in the elderly. Semin Nephrol 1996;16:319-29.  Back to cited text no. 8      
9.Leblanc A, Caillaud JM, Hartmann O, et al. Hy-percalcemia preferentially occurs in unusual forms of childhood non-Hodgkin′s lymphoma, rhabdo-myosarcoma, and Wilms′ tumor. A study of 11 cases. Cancer 1984;54:2132-6.  Back to cited text no. 9      
10.Ritch PS. Treatment of cancer-related hypercal-cemia. Semin Oncol 1990;17:26-33.  Back to cited text no. 10      
11.Stewart AF. Hypercalcemia associated with cancer. N Engl J Med 2005;352:373-9.  Back to cited text no. 11      
12.Farias ML. Hypercalcemia of Malignancy: Cli-nical Features, Diagnosis and Treatment. Arq Bras Endocrinol Metab 2005;49:816-24.  Back to cited text no. 12      
13.Giuliani N, Bataille R, Mancini C, Lazzaretti M, Barille S. Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood 2001;98: 3527-33.  Back to cited text no. 13      
14.Clines GA, Guise TA. Hypercalcemia in hemato-logic malignancies and in solid tumors associated with extensive localized bone destruction. In: Favus MF, (ed). Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 5th ed. Washington D.C. American Society for Bone and Mineral Research, 2003, 251-6.  Back to cited text no. 14      
15.Horwitz MJ, Stewart AF. Humoral hypercalcemia of malignancy. In: Favus MF (ed). Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 5th ed. Washington D.C. American Society for Bone and Mineral Research, 2003:246--50.  Back to cited text no. 15      
16.Syed MA, Horwitz MJ, Tedesco MB, Garcia-Ocana A, Wisniewski SR, Stewart AF. Parathy-roid hormone-related protein-(1-36) stimulates renal calcium reabsorption in normal human vo-lunteers: implications for the pathogenesis of humoral hypercalcemia of malignancy. J Clin Endocrinol Metab 2001;86:1525-31.  Back to cited text no. 16      
17.Fierabracci P, Pinchera A, Miccoli P, et al. Increased prevalence of primary hyperparathyroidism in treated breast cancer. J Endocrinol Invest 2001;24: 315-20.  Back to cited text no. 17      
18.Hewison M, Kantorovich V, Liker HR, et al. Vita-min D-mediated hypercalcemia in lymphoma: Evi-dence for hormone production by tumor-adjacent macrophages. J Bone Miner Res 2003;18:579-82.  Back to cited text no. 18      
19.Spinazz´e S, Schrijvers D. Metabolic emergencies. Crit Rev Oncol Hematol 2006;58:79-89.  Back to cited text no. 19      
20.Sands JM, Naruse M, Baum M, et al. Apical extra-cellular calcium/polyvalent cation sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct. J Clin Invest 1997;99:1399-405.  Back to cited text no. 20      
21.Barnett ML. Hypercalcemia. Semin Oncol Nurs 1999;15:190-201.  Back to cited text no. 21      
22.LeBoff MS, Mikulec KH. Hypercalcemia: clini-cal manifestations, pathogenesis, diagnosis, and manage-ment. In: Favus MF (ed). Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabo-lism. 5th ed. Washington D.C. American Society for Bone and Mineral Research, 2003;225-30.  Back to cited text no. 22      
23.De Marco LA, Liberman B Water metabolism and diabetes insipidus. In: Cukiert A, Liberman B (eds). Clinical and surgical neuroendocrinology. 1st ed. Sao Paulo. Editora Lemos, 2002, 563-76.  Back to cited text no. 23      
24.Jackson EK. Drugs affecting renal and cardiovascu-lar function. In: Hardman JG, Limbird LE, Gilman AG, (eds). The pharmacological basis of thera-peutics. 10th ed. New York. McGraw Hill, 2001, 793-5.  Back to cited text no. 24      
25.Reeves WB, Bichet DG, Andreolli TE. The poste-rior pituitary and water metabolism. In: Wilson JD, Fotser DW, Kronemberg HM, Larsen PR (eds). Williams textbook of endocrinology. 9th ed. Phila-delphia. WB Saunders, 1998;341-87.  Back to cited text no. 25      
26.Vilar L, Leal E. Diabetes insipidus - Diagnosis and treatment. In: Vilar L, Castellar E, Moura E, et al, (eds). Clinical endocrinology. 2nd ed. Rio de Janeiro. Medsi, 2001;103-24.  Back to cited text no. 26      
27.Fouqueray B, Paillard F, Baud L. Polyuropolydipsic syndromes. Presse Med 1998;27:45-53.  Back to cited text no. 27      
28.Casulari LA, Costa KN, Albuquerque RC, Naves LA, Suzuki K, Domingues L. Differential diagnosis and treatment of hyponatremia following routine pituitary surgery. J Neurosurg Sci 2004; 48:11-18.  Back to cited text no. 28      
29.Taylor SL, Tyrrell JB, Wilson CB. Delayed onset of hyponatremia after transsphenoidal surgery for pituitary adenomas. Neurosurgery 1995; 37:649-54.  Back to cited text no. 29      
30.Whitaker SJ, Meanock CI, Turner GF, et al. Fluid balance and secretion of antidiuretic hormone fo-llowing transsphenoidal pituitary surgery: A prelimi-nary series. J Neurosurg 1985;63:404-12.  Back to cited text no. 30      
31.Oliveira S Jr, Vilar L, Cavalcanti N. Management of the syndrome of inappropriate secretion of ADH. In: Vilar L, Castellar E, Moura E, et al (eds). Cli-nical endocrinology. 2nd ed. Rio de Janeiro. Medsi, 2001;125-34  Back to cited text no. 31      
32.Sorensen JB, Andersen MK, Hansen HH. Syn-drome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant disease. J Intern Med 1995;238:97-110.  Back to cited text no. 32      
33.Verbalis JG. Tumoral hyponatremia. Arch Intern Med 1986;146:1686-7.  Back to cited text no. 33      
34.Olson BR, Gumowski J, Rubino D, Oldfield EH. Pathophysiology of hyponatremia after transsphe-noidal pituitary surgery. J Neurosurg 1997;87:499--507.  Back to cited text no. 34      
35.Olson BR, Rubino D, Gumowski J, Oldfield EH. Isolated hyponatremia after transsphenoidal pitui-tary surgery. J Clin Endocrinol Metab 1995; 80: 85-91.  Back to cited text no. 35      
36.Riggs JE. Neurologic manifestation of electrolyte disturbances. Neurol Clin 2002;20:227-39.  Back to cited text no. 36      
37.Sane T, Rantakari K, Poranen A, Tahtela R, Vali-maki M, Pelkonen R. Hyponatremia after trans-sphenoidal surgery for pituitary tumors. J Clin Endocrinol Metab 1994;79:1395-8.  Back to cited text no. 37      
38.Vilar L, Leal E, Oliveira S, Lyra R. Alterations of the vasopressin. In: Coronho V, Petroianu A, Santana EM, Pimenta LG (eds). Textbook of endocrino-logy and endocrine surgery. Belo Horizonte. Guanabara-Koogan, 2001;316-33.  Back to cited text no. 38      
39.Bouloux PM. Investigation of hypothalamo-pitui-tary disorders. In: Bouloux PM, Rees LH (eds). Diagnostic tests in endocrinology and diabetes. London. Chapman& Hall Medical, 1994, 20-30.  Back to cited text no. 39      
40.Seegmiller JE, Laster L, Howell RR. Biochemistry of uric acid and its relation to gout. N Engl J Med 1963;268:712-6.  Back to cited text no. 40      
41.Hande KR, Garrow GC. Acute tumor lysis syn-drome in patients with high-grade non-Hodgkin′s lymphoma. Am J Med 1993;94:133-9.  Back to cited text no. 41      
42.Flombaum CD. Metabolic emergencies in the cancer patient. Semin Oncol 2000;27(3):322-34.  Back to cited text no. 42      
43.Cancela CS, Rezende PV, Oliveira BM. Tumor lysis syndrome [internet]. Belo Horizonte: Scientific texts of the pediatric society of Minas Gerais. 2007 - (cited in 30/11/2008). Available from: http://www.smp.org.br/downloads/tumoral.pdf.  Back to cited text no. 43      
44.Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor Lysis syndrome: An evidence-based review. J Clin Oncol 2008;26:2767-78.  Back to cited text no. 44      
45.Oliveira BM, Viana MB. Oncohematological emer-gencies. In: Simoes e Silva AC, Norton RC, Mota JAC, Pena FJ (eds). Urgence manual in pediatry. Rio de Janeiro. Medsi, 2003,456  Back to cited text no. 45      
46.Kawai M, Sahashi K, Yamase H, Kishida Y, Sumida K, Kawamura K. Renin-producing adrenal tumor: report of a case. Surg Today 1998;28:974-8.  Back to cited text no. 46      
47.Wong L, Hsu TH, Perlroth MG, Hofmann LV, Haynes CM, Katznelson L. Reninoma: Case re-port and literature review. J Hypertens 2008;26: 368-73.  Back to cited text no. 47      
48.Shimamoto K, Takizawa H. Juxtaglomerular cell tumor overview of rennin-producing tumors (in Japanese). Horumon To Rinshou (Clin Endocri-nol) 1994;42:283-8.  Back to cited text no. 48      
49.Stephen MR, Lindop GB. A renin secreting ova-rian steroid cell tumour associated with secondary polycythaemia. J Clin Pathol 1998;51:75-82.  Back to cited text no. 49      
50.Anderson PW, Macaulay L, Do YS, et al. Extra-renal reninsecreting tumors: Insights into hyper-tension and ovarian renin production. Medicine 1989;68:257-68.  Back to cited text no. 50      
51.Corry DB, Tuck ML. Secondary aldosteronism. Endocrinol Metab Clin North Am 1995;24:511-29.   Back to cited text no. 51      
52.Corvol P. Tumor dependent hypertension. Hyper-tension 1984;6:593-6.  Back to cited text no. 52      
53.Laragh J. Laragh′s lessons in pathophysiology and clinical pearls for treating hypertension. Am J Hypertens 2001;14:837-54.  Back to cited text no. 53      
54.Galloway J. Remarks on Hodgkin′s disease. Br Med J 1922;2:1201-4.  Back to cited text no. 54      
55.Davison AM. Renal diseases associated with ma-lignancies. Nephrol Dial Transplant 2001;16:3-4.  Back to cited text no. 55      
56.Sawyer N, Wadsworth J, Winnen M, Gabriel R. Prevalence, concentration and prognostic impor-tance of proteinuria in patients with malign-nancies. Br Med J 1988;296:295-8.  Back to cited text no. 56      
57.O′Callaghan CA, Hicks J, Doll H, Sacks SH, Cameron JS. Characteristics and outcome of mem-branous nephropathy in older patients. Int Urol Nephrol 2002;33:157-65.  Back to cited text no. 57      
58.Egen JW, Lewis EJ. Glomerulopathies in neo-plasia. Kidney Int 1977;11:297-306.  Back to cited text no. 58      
59.Bacchetta J, Juillard L, Cochat P, Droz JP. Para-neoplastic glomerular diseases and malignancies. Crit Rev Oncol Hematol (internet) 2008 (cited in 30/11/2008). Available from: http://www.sciencedirect.com/science/journal/104 08428 OI:10.1016/j.critrevonc.2008. 08. 003.  Back to cited text no. 59      
60.Mallouk A, Pham PT, Pham PC. Concurrent FSGS and Hodgkin′s lymphoma: Case report and litera-ture review on the link between nephrotic glome-rulopathies and hematologycal malignancies. Clin Exp Nephrol 2006;10:284-9.  Back to cited text no. 60      
61.Lefaucheur C, Stengel B, Nochy D, et al. Mem-branous nephropathy and cancer: epidemiologic evidence and determinants of high risk cancer association. Kidney Int 2006;70:1510-7.  Back to cited text no. 61      
62.Burstein DM, Korbet SM, Schwartz MM. Mem-branous glomerulonephritis and malignancy. Am J Kidney Dis 1993;22:5-10.  Back to cited text no. 62      
63.Magyarlaki T, Kiss B, Buzogany I, Fazekas A, Sukosd F, Nagy J. Renal cell carcinoma and para-neoplastic IgA nephropathy. Nephron 1999;82: 127-30.  Back to cited text no. 63      
64.Feriozzi S, Giannakakis K, Ranalli TV, et al. Cres-centic glomerulonephritis associated with nonrenal malignancies. Am J Nephrol 1984;4:208-14.  Back to cited text no. 64      
65.Pankhurst T, Savage CO, Gordon C, Harper L. Malignancy is increased in ANCA-associated vasculitis. Rheumatology (Oxford) 2004;43:1532-5.  Back to cited text no. 65      
66.Werner TL, Agarwal N, Carney HM, Rodgers GM. Management of cancer-associated thrombotic microangiopathy: What is the right approach? Am J Hematol 2007;82:295-8.  Back to cited text no. 66      

Correspondence Address:
Pedro Henrique de Oliveira Filgueira
Department of Internal Medicine, Division of Nephrology, Walter Cantidio University Hospital, Federal University of Ceara CEP: 60125-001
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