| Abstract|| |
We report a 20-year-old man who presented to our emergency room with a history of polyuria, weakness, constipation, nausea, and vomiting of two months duration. History and clinical examination revealed a significant weight loss and mild hepatomegaly. Laboratory investigations revealed hypokalemia, hypernatremia, and severe metabolic acidosis and anemia. Ultra-sound of the abdomen revealed enlarged kidneys without hydronerphrosis. The patient developed paralysis due to further decline in serum potassium level, which improved after an aggressive fluid and electrolyte management. He was investigated extensively for polyuria and type of acidosis. The kidney biopsy showed interstitial leukemic infiltration. He was managed accordingly and recovered from the condition. This case demonstrates an unusual presentation of a hematological malignancy, which was a diagnostic as well as a management challenge.
|How to cite this article:|
Imtiaz S, Qayyum S, Kafouri H, Habib ur Rehman, Al Khoiter M, Askar A. A young man with polyuria and lethargy. Saudi J Kidney Dis Transpl 2011;22:847-52
|How to cite this URL:|
Imtiaz S, Qayyum S, Kafouri H, Habib ur Rehman, Al Khoiter M, Askar A. A young man with polyuria and lethargy. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2021 Mar 6];22:847-52. Available from: https://www.sjkdt.org/text.asp?2011/22/4/847/82745
| Introduction|| |
Acute lymphoblastic leukemia is a common hematological malignancy and is highly responsive to chemotherapy, but renal involvement is rarely seen in clinical practice. It usually presents with kidney enlargement or tumor lysis syndrome with electrolyte abnormalities. , Renal tubular acidosis and diabetes insipidus are very rare manifestations of acute lympho-blastic leukemia and form a diagnostic as well as management challenge. Since the prognosis after the treatment is good and the overall 5-year survival rate is 80-86% and 5-year event free survival rate is 78-83%,  early diagnosis and prompt and aggressive management to save the patient from acute fluid and electrolytes and acid base abnormality is very crucial.
| Case Report|| |
A 20-year-old Saudi man, a secondary school student and a football player who was previously healthy, presented to the emergency room of our hospital with complaints of progressive fatigue and lethargy of three months duration, constipation for two weeks, and nausea and vomiting of three days duration. He started to feel generalized nonspecific weakness, which was progressive and forced him to take more rest at the least effort, and it was associated with polydipsia and polyuria, and nocturia. Finally, the complaint of nausea and vomiting forced him to visit the emergency room. He had persistent vomiting, about ten episodes in one day, before coming to hospital. He admitted to a 5-kg weight loss within the last six months. He also had feverish feeling, especially in the evening, but never documented any rise in temperature.
The patient's past medical history was unremarkable for head trauma or use of any medications. Family history was unremarkable except that his father was a diabetic.
Examination revealed a young gentleman looking pale, lethargic, and weak, but alert and oriented to time, space, and person; his BP was 100/60 and pulse was 110 beats/minute. Systemic examination was remarkable for a palpable edge of the liver with an increase of span, but it was smooth, firm, and non-tender. From his clinical presentation, a differential diagnosis of diabetes insipidus, diabetes mellitus and psychogenic polydipsia was made and the initial investigations revealed the following: blood glucose: 4.5 mmol/L, urea: 4.8 mmol/L, creatinine: 196 μmol/L, sodium: 149 mmol/L, potassium: 2.9 mmol/L, chloride: 126 mmol/L, calcium: 2.6 mmol/L, lactate: 9.4 mmol/L, uric acid: 84 μmol/L, phosphorus: 0.9 mmol/L, bicarbonate: 7.0 mmol/L, Hb: 75 g/L, MCV: 80, platelets: 1,600,000, and WBC: 7,500 cells/μL and normal differential count. The peripheral film was normal.
After reviewing the investigations, diabetes mellitus and psychogenic polydipsia were excluded, while the elevated serum sodium suggested diabetes insipidus. The other biochemical abnormalities which were worth noting included a high serum creatinine that reached 129 μmol/L after hydration, high serum calcium that normalized with hydration, low levels of serum potassium, serum uric acid, serum bicarbonate, borderline serum phosphorus, and high levels of serum lactate besides severe anemia and high platelet count. The urinary osmolality in a spot urine exam was 201 mosm/kg and appeared very low in context with high plasma osmolality of 308 mosm/ kg, and the electrolyte levels in the urine included sodium: 51 mmol/L, potassium: 26 mmol/L, and chloride: 53 mmol/L with a urinary anion gap of +24.
All this suggested diabetes insipidus. Due to the clinical condition of the patient and a continuous high requirement of intravenous potassium, a formal water deprivation test was difficult to perform. He was started on antidiuretic hormone (DDAVP) 2 μg subcutaneously, which was increased to 4 μg, but the urinary output never decreased below 4,000 mL/day, so it was discontinued. In the meanwhile, a magnetic resonance imaging (MRI) scan of the pituitary gland was performed in search of any brain lesion. [Figure 1]a shows an MRI of a normal individual, with high intensity signals in the posterior pituitary gland that suggest the presence of secretory granules containing ADH, while in our patient this signal was absent [Figure 1]b. The MRI did not reveal any mass lesion, Other differential diagnosis was nephrogenic diabetes insipidus (NDI), which has different causes as shown in [Table 1]. Lithium, demeclocycline, protein malnutrition, sickle cell disease, and hypercalcemia as causes of NDI were excluded by the patient's history and laboratory investigations. The conditions that required further evaluation included chronic renal insufficiency and persistent hypokalemia despite intensive therapy. In addition, the anemia on presentation did not correlate with the degree of his kidney dysfunction and needed further evaluation.
|Figure 1: a: T1 sagittal image showing high intensity in posterior pituitary gland secondary to the presence of secretory granules in a normal subject.|
Figure 1: b: T1 sagittal image shows a loss of high signal intensity in the posterior pituitary gland suggesting diabetes insidipus or effect of dehydration.
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The serum bicarbonate was very low and serum lactate was very high. To evaluate them further, an arterial blood gas was performed and revealed the following values: pH 7.077; PCO 2 29.1 mmHg; PO 2 97 mmHg; HCO 3 8.4 mmol/L; and total CO 2 9.3 mmol/L. The calculated anion gap was normal: 149 - 126 + 8 = 15.
The arterial blood gas was compatible with severe metabolic acidosis and normal anion gap, and the causes could be renal and non-renal. A positive urinary anion gap favored renal to non-renal causes of acidosis.
The urinalysis revealed the following: urinary pH of 6.0, +1 proteinuria, glucosuria +2, and specific gravity 1.010. The 24-hour proteinuria was 3.4 g.
The gross abnormalities in the patient's electrolytes were evaluated further by a 24-hour urinary electrolytes analysis and it revealed interesting facts [Table 2]. There was a very high urinary potassium excretion along with high urinary calcium and magnesium excretion, compatible with a gross tubular defect. His urinary potassium was further calculated by fractional excretion of potassium, which also showed a high excretion rate.
The tubular acidosis in this patient was compatible with both proximal and distal disorders.
There was a disparity between the dipstick proteinuria and 24-hour urinary proteins, which was cleared by performing urinary protein electrophoresis that revealed a very high percentage of globulins (75%) and suggested a possibility of a lymphoproliferative disorder such as multiple myeloma, lymphoma or leukemia [Table 3].
An ultrasound of the kidneys showed grossly enlarged both kidneys with preserved corticomedullary differentiation with no hydronephrosis [Figure 2].
|Figure 2: Ultrasound of the kidneys was done shows grossly and diffusely enlarged both kidneys with preserved corticomedullarydifferentiation with no hydronephrosis.|
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The findings on the ultrasound of the kidneys, the unexplained high serum creatinine, the severe unexplained anemia, and the severe proteinuria dictated us to proceed for a kidney biopsy and a bone marrow biopsy.
The kidney biopsy revealed minimal mesangial expansion in all the glomeruli, while the interstitium was expended by dense atypical lymphoid infiltrate. The infiltrate did not destroy the intervening tubules and glomeruli. Immunohistochemistry showed atypical cells with diffuse positivity with CD3 staining [Figure 3]a, b, and c.
|Figure 3: a: (H & E) All glomeruli show minimal mesangial expansion. Interstitium is expended by dense atypical lymphoid infiltrate. The infiltrate is not destroying the intervening tubules and glomeruli.|
Figure 3: b: Massive cortical infiltration of atypical lymphocytes high magnification.
Figure 3: c: Trichrome staining of the kidney biopsy.
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The bone marrow biopsy revealed the presence of diffuse and heavy infiltration of lymphoid looking mononuclear cells, which were variable in size. Immunophenotyping of the bone biopsy showed blast cells negative for CD34, HLA DR surface IgM, CD79b, FMC 7, CD23, CD21, CD4, CD8, CD3, myeloid and B-lymphoid markers, but positive for CD5, CD7, CD10, CD43, CD99 with partial clonality for TCR (alpha and beta) [Figure 4] a, b, and c.
|Figure 4: a: Bone marrow shows diffuse and heavy infiltration of lymphoid looking mononuclear cells which are variable in size.|
Figure 4: b: The mononuclear cells are positive for CD45, CD3, CD7, CD5, BC1-2 and Ki-67(80%).
Figure 4: c: The mononuclear cells are negative for CD34, TdT, CD20, CD10, BCL-6, CD23, CD79a, Kappa, Lambda, CD30 and MPO.
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The findings of the kidney and bone marrow biopsies were compatible with acute T cell lymphocytic leukemia.
The hospital course of the patient was very fulminant. His volume depletion was treated with normal saline. His serum potassium did not respond to intravenous repletion, and he developed severe skeletal muscle paralysis, along with paralytic ilieus. He was transferred to the intensive care unit to monitor any repiratory paralysis, and potassium was infused through a central venous line. The acidosis was partially corrected despite continuous infusion of intravenous sodium bicarbonate. After diagnosis, he was referred to the oncologist for consultation about further management. He received bone marrow transplantation and recovered from all symptoms of NDI and renal tubular acidosis.
| Discussion|| |
This case demonstrates a unique presentation of acute lymphoblastic leukemia due to severe infiltration of the tumor cells into the renal interstitium and tubules. The patient presented with features of both distal and proximal renal tubular acidosis due to indiscriminate infiltration of tumor cells in every part of renal parenchyma except glomeruli.
The effects of the hematologic neoplasia on the kidney include direct invasion, glomerulopathies, tubulointerstitial disease, and fluid and electrolyte imbalance. Leukemia has more predilections to kidney compared with lymphoma. 
Lactic acidosis and hypokalemia due to tubular dysfunction were also associated with acute leukemia in the pediatric population. 
Renal enlargement on presentation due to tumor cells has not been studied in adult but mostly in pediatric population. Earlier, the enlarged kidneys were supposed to be associated with poor prognosis, in term of shorter duration of first remission and shorter event free survival.  Later on, studies showed no difference in survival, probably due to better care of the cancer patients and new and potent chemotherapy. 
Tubular dysfunction resulting in metabolic acidosis and DNI has also been reported with multiple myeloma and myelodysplastic syndrome during treatment with Amphoterecin B.  The tumor cells usually indiscriminately involve both the proximal and distal tubules and the interstitium and may promote severe electrolyte and acid base abnormalities as we encountered in our patient.
Hypokalemia is an important cause of reversible NDI through multiple pathological mechanisms including disturbance of the generation of medullary interstitial tonicity,  defect in cyclic AMP generation, and downregulation of aquaporin 2 channels. 
Our case demonstrates an unusual presentation of a hematological malignancy, which was a diagnostic as well as a management challenge.
| Questions and Answers|| |
Dr. Azhari Osman Al-Hassan (Chairman of RNTC, Security Forces Hospital, Riyadh):
The floor is open for discussion and questions.
Audience: The electrolyte and fluid disturbances were challenging in this case. What are the priorities in the management in such cases?
Dr. Salman Imtiaz (Presenter, King Khalid University Hospital): Stabilizing the patient is of utmost importance before any further management. Polyuria and hypokalemia were challenging in our case because of the choice of the appropriate fluids. The patient was symptomatic and required massive amounts of K + supplementation. Normal saline was more appropriate than bicarbonate because the latter would shift the K + inside the body cells and osmolality should be monitored closely for any changes in the osmolality to switch to half normal or D5W in case needed. The DDAVP did not help in this regard.
Audience: Severe anemia was remarkable in this case, and with the presence of volume depletion, the level of hemoglobin should be worse. Was raising the level addressed before the contemplation of kidney and bone marrow biopsies?
Dr. Imtiaz: Yes. We transfused the patient to raise the hemoglobin to an appropriate level before the investigative procedures.
Audience: The severe anemia imposed a relative risk on performing a kidney biopsy. Would it not be better to perform the bone marrow biopsy or aspiration first to diagnose the cause of anemia that would have led to the final diagnosis of leukemia?
Dr. Imtiaz: You are right. However, in the presence of the renal manifestations of polyuria, acidosis, and hypokalemia, the histological diagnosis was necessary, especially in the face of indecisive ultrasound of the kidneys.
Audience: The presence of acidosis complicated the picture. The treatment with sodium bicarbonate would worsen the hypokalemia. Would you prefer to withhold or treat with sodium bicarbonate?
Dr. Imtiaz: We treated the patient initially with sodium bicarbonate, but the further drop of the K + blood levels to dangerous levels swayed us away from it and we kept monitoring the patient's total CO 2 hoping for improvement with the fluid replacement and K + supplementation.
Dr. Azhari: Thank you all for joining us tonight.
| References|| |
|1.||Banday KA, Sirwal IA, Reshi AR. Renal involvement in hematological neoplasia. Indian J Nephrol 2004;14:50-2. |
|2.||Mohammad H, Ashok S. Acute lymphoblastic leukemia presenting with lactic acidosis and renal tubular dysfunction: J Pediatr Hem Oncol 2003;25(6):488-90. |
|3.||Winick NJ, Carroll W, Hunger SP. Child hood leukemia: new advantages and challenges. N Eng J Med 2004;351(6):601-3. |
|4.||Hann IM, Lees PD, Palmer MK, Gupta S, Morris-Jones PH. Renal size as a prognostic factor in child hood acute lymphoblastic leukemia. Cancer 1981;48(1):207-9. |
|5.||D´Angelo P, Mura R, Rizzari C, et al. Prognostic value of nephromegaly at diagnosis of childhood acute lymphoblastic leukemia. Acta Haematol 1995;94(2):84-9. |
|6.||Hoorn EJ, Zietse R. Combined renal tubular acidosis and diabetes insipidus in hematological disease. Nat Clin Pract Nephrol 2007;3: 171-5. |
|7.||Elkajaer M, Kown T, Wang W, Nielsen J. Altered expression of renal NHE3, TSC, BSC-1 and ENaC subunits in potassium depleted rats. Am J Physiol Renal Physiol 2002;283: F1376-88. |
|8.||Marples D, Frokiaer J, Dourp J. Hypokalemia-induced down regulation of Aquaporin-2 water channels expression in rat kidney medulla and cortex. J Clin Invest 1996;97:1960-8. |
King Khalid University Hospital, King Saud University, P.O. Box 71449, Postal code 11587, Riyadh
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]