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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 1  |  Page : 67-71
Interstitial and Glomerular Renal Involvement in Sarcoidosis

1 Department of Internal Medicine and Nephrology, Charles Nicolle Hospital, Tunis, Tunisia
2 Laboratoire Sante 02, Charles Nicolle Hospital, Tunis, Tunisia

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Sarcoidosis is a systemic disease characterized by chronic granulomatous inflammation. Chronic kidney disease (CKD) was reported in less than 1% of patients of sarcoidosis. The prevalence of tubulo-interstitial nephritis (TIN) in sarcoidosis varies from 7 to 27%. In this retrospective study, we present 15 patients with interstitial or glomerular renal involvement secondary to sarcoidosis diagnosed in our center from 1975 to 2006. Patients were 13 (96.6%) females and two males with a mean age of 56.5 years. CKD was present in 14(93.3%) patients, proteinuria in 13(96.6%), and nephrotic syndrome in one. Pulmonary involvement was present in 10 (66.6%) patients. Renal biopsy performed in 12 (80%) patients revealed TIN lesions in 10 (66.6%) patients, extracapillary proliferative glomerulonephritis (GN) in one, and membranous GN type 2 in another. Corticosteroid therapy using prednisolone 0.5 to 1 mg/kg per day was used in 12(80%) patients. Ten (66.6%) patients were followed up for a mean period of 25 months (ranged from 2 to 48 months). The outcome was favorable with 7 (46.6%) patients improved their renal function, 6 (40%) remained with a moderate CKD, one normalized his renal function, and one died suddenly after 2 months of initiating the treatment corticosteroids. We conclude that corticosteroid treatment is efficient in TIN and variably efficient in GN. Patients with sarcoidosis may cause advanced renal failure, which renders it a serious nephrological condition.

Keywords: Sarcoidosis, Glomerulonephritis, Tubulo-interstitial nephritis

How to cite this article:
Kaaroud H, Fatma LB, Beji S, Jeribi A, Maiz H B, Moussa FB, Goucha R, Turki S, Kheder A. Interstitial and Glomerular Renal Involvement in Sarcoidosis. Saudi J Kidney Dis Transpl 2008;19:67-71

How to cite this URL:
Kaaroud H, Fatma LB, Beji S, Jeribi A, Maiz H B, Moussa FB, Goucha R, Turki S, Kheder A. Interstitial and Glomerular Renal Involvement in Sarcoidosis. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2020 Nov 27];19:67-71. Available from: https://www.sjkdt.org/text.asp?2008/19/1/67/37436

   Introduction Top

Sarcoidosis is a systemic disease charac­terized by chronic granulomatous inflamma­tion. [1],[2] The most common clinical features are pulmonary, and skin lesions. [1] Renal disease in sarcoidosis is rare due to nephrocalcinosis and or nephrolithiasis related to hypercalciuria. [3],[4]

In this study, we present 15 patients with sarcoidosis and renal interstitial, or glomerular involvement.

   Materials and Methods Top

Using a computerized database, we reviewed retrospectively from 1975 to 2006 patients diagnosed as sarcoidosis with renal involve­ment that included interstitial or glomerular injury. We excluded from the analysis all patients with nephrocalcinosis or nephro­lithiasis. We analysed clinical features (pul­monary, ophthalmic, skin involvement), phy­sical examination, laboratory tests (renal function, liver function tests, corrected cal­cium, serum globulins, and urinary 24 hours protein excretion), studies for  Mycobacterium tuberculosis Scientific Name Search B) including tuberculin tests, TB sputum culture, radiological tests (chest X-ray, abdominal ultrasound and compute­rized tomography scan), bronchoscopy, bron­chus biopsy, bronchoalveolar lavage, salivary glands biopsy, and renal biopsy.

   Results Top

We studied the records of 15 patients diag­nosed as sarcoidosis with non nephrocalci­nosis non-nephrolithiasis renal involvement. Thirteen patients (96.6%) were females and two patients were males with a mean age of 56.5 years (range from 19 to 83 years). Cli­nical, biologic, histological features, treat­ment and follow-up periods are shown in [Table - 1].

Clinical manifestations were proteinuria in 13 (96.6%) patients, hematuria in 6 (40%) patients and high blood pressure in six (40%) patients. Pulmonary involvement was present in 10 (66.6%) patients with pulmonary inters­titial syndrome in 8 (53%) patients, and mediastinal lymph node in 4 (27%) patients. Broncho-alveolar lavage showed in 6 (40%) patients a high index of lymphocysts. Peri­pheral lymph nodes were present in 2 patients, axillary and jugular in one patient and mesen­teric in another.

Chronic kidney disease (CKD) was revealed in 14 (93.3%) patients with a mean serum creatinine of 460 µmol/L (ranged from 138 to 1215 µmol/L), While one patient had normal renal function. Elevated serum calcium was noted in 3 (21%) patients with a mean level of 3.12 mmol/L. Elevated erythrocytes sedimentation rates were revealed in 12 (80%) patients with a mean of 107 mm the first hour, and gamma globulin levels with a mean of 16.3 g/L. Liver cholestase was present in one patient with liver granulomas. Serum angiotensin-converting enzyme (ACE) level was checked in 2 patients, but was elevated in one to a level of 205 units. Urinary 24 hours protein excretion was measured in 13 (96.6%) patients with a mean level of 1.23g/24 hours (ranged from 0.2 to 3.6 g/24 hours). Nephrotic syndrome was present in one patients with urinary 24 hours proteinuria of 3.6 g/24 hours.

Tuberculosis screening was performed in most patients including the tuberculin test, which was negative in 12 (80%) patients. Urine and sputum culture for TB was nega­tive in all patients. Chest-X-ray showed pulmonary interstitial syndrome in 8 (53%) patients, and mediastinal lymph nodes in 4 (27%) patients.

Renal biopsies performed in 12 (80%) pa­tients revealed tubulo-interstitial lesions in 10 (66.6%) patients, extra-capillary proli­ferative glomerulonephritis(GN) in one, and membranous GN type 2 in another. Salivary gland biopsy performed in 5 (33.3%) patients revealed lymphoplasmocyts infiltrate in 2 patients. A liver biopsy showed sarcoidosic granuloma in one patient.

Corticosteroid therapy with prednisolone 0.5 to 1 mg/kg per day was administered in 12 (80%) patients. In one patient, cyclophos­phamide was added to prednisolone because of retinal vasculitis. One patient with end­stage renal disease necessitated chronic hemodialysis. Ten (66.6%) patients were fo­llowed up for a mean period of 25 months (range from 2 to 48 months).

The outcome was favorable with 7 (46.6%) patients improved their renal function, 6 (40%) remained with a moderate CKD, one normalized his renal function, and one died suddenly after 2 months of initiating the treatment corticosteroids.

   Discussion Top

Sarcoidosis typically affects young adults with the same rate in males and females. Renal failure in sarcoidosis may occur as a consequence of hypocalcemia or hypercal­ciuria, glomerular disease or granulomatous interstitial nephritis. [5] Chronic kidney disease (CKD) was reported in less than 1% of patients in sarcoidosis, and it seems to be more frequent in older patients.

As reported in a few patients in the litera­ture, the impairment renal function resulted in the diagnosis of sarcoidosis in our patients. [6],[7],[8],[9],[10],[11],[12] In sarcoidosis, hypercalciuria may be present in half of the patients, whereas only 10 to 20% have hypercalcemia. [3],[5] Hyper­calcemia is due to increased intestinal absorp­tion of calcium related to increased levels of calcitriol. Patients with sarcoidosis commonly have elevated levels of angiotensin conver­ting enzyme (ACE). [13] As calcitriol, ACE is a product of epitheloid cells within the granuloma. Serum ACE was elevated in one patient in our study.

Granulomatous interstitial nephritis is common in sarcoidosis, and was first documented in 1933. [14],[15],[16] The prevalence has been estimated from post-mortem series, and reports vary from 7 to 27%. [16],[17] In our study, 80% of the patients had TIN, and 47% with granuloma. As in almost patients cited in the literature, most of our patients pre­sented with advanced CKD, which may be severe enough to require dialysis at least transiently. [3] Glomerular involvement in sarcoidosis may manifest as focal segmental sclerosis, membranous GN, mesangiopro­liferative GN, mesangiocapillary GN, and IgA GN, although their mechanisms are not known. [18] Crescentic GN associated with sarcoidosis is very rare, [17],[18],[19] as was revealed in our seventh patient.

Corticosteroid treatment is efficient in TIN. [3] In our study, this treatment was used in 57% TIN patients with normalization of renal function in 6% and improvement of renal function in 33.3% patients.

Corticosteroid treatment is variably efficient in GN depending on its pathological type. As observed in idiopathic form, the membranous GN associated with sarcoidosis has high rate of resistance to corticosteroid treatment. That was the result in our two patients with membranous GN treated by corticosteroid.

The relapse in patients who respond to treatment can be retreated and respond again to another course of corticosteroid. [3] In our patients, no relapse was noted.

We conclude that sarcoidosis is a multi­system granulomatous disorder of unknown cause. Granulomatous interstitial nephritis is more common than glomerular involvement. Most patients may develop advanced renal failure. Sarcoidosis cannot necessary be con­sidered a benign nephrological disease.

   References Top

1.Robson MG, Banerjee D, Hopster D, Cairns HS. Seven patients of granulomatous inters­titial nephritis in the absence of extrarenal sarcoid. Nephrol Dial Transplant 2003;18: 280-4.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.James DG. Descriptive definition and historic aspects of sarcoidosis. Clin Chest Med 1997;18:663-79.  Back to cited text no. 2  [PUBMED]  
3.Hannedouche T, Grateau G, Noel LH, et al. Renal granulomatous sarcoidosis: report of six patients. Nephrol Dial Transplant 1990;5:18-24.  Back to cited text no. 3    
4.Glassock RJ. Sarcoidosis. In: Massy SG, Glassocks RJ, eds. Textbook of nephrology. Williams and Wilkins: Baltimore; 1983. p. 6176-8.  Back to cited text no. 4    
5.Gobel U, Kettritz R, Schneider W, Luft FC. The protean face of renal sarcoidosis. J Am Soc Nephrol 2001;12:616-23.  Back to cited text no. 5    
6.Sorger K, Taylor WA. Generalized sarcoidosis. Arch Pathol 1961;71:35-43.  Back to cited text no. 6    
7.Bolton WK, Atuk NO, Rametta C, et al. Reversible renal failure from isolated granulomatous renal sarcoidosis. Clin Nephrol 1976;5:88-92.  Back to cited text no. 7  [PUBMED]  
8.Barbiano di Belgiojoso GB, Bertoli S, Confalonieri R, et al. Granulomatous interstitial nephritis with isolated manifestation of sarcoidosis: Report of a patients EDTA. Proc Eur Dial Transplant Assoc 1980;27.  Back to cited text no. 8    
9.Allegri L, OlivettiG, David S, et al. Sarcoid granulomatous nephritis with isolated and reversible renal failure. Nephron 1980;25:207-8.  Back to cited text no. 9    
10.Alcazar JM, Bello I, Arteaga J, et al. Sarcoidosis and renal failure. Nephron 1981;29:281.  Back to cited text no. 10  [PUBMED]  
11.Hagege A, Baglin A, Princeau J, et al. Sarcoidosis disclosed by renal insufficiency (3 cases). Sem Hop 1983;59:2823-6  Back to cited text no. 11    
12.Williams PF, Thomson D, Anderton JL. Reversible renal failure due to isolated renal sarcoidosis. Nephron 1984;37:246-9.  Back to cited text no. 12  [PUBMED]  
13.Study PR, Bird R. Serum angiotensin converting enzyme in sarcoidosis: Its value in present clinical practice. Ann Clin Biochem 1989;26:13-8.  Back to cited text no. 13    
14.Branson JH, Park JH. Sarcoidosis hepatic involvement: Presentation of a patients with fatal liver involvement including autopsy findings and review of evidence of sarcoid involvement of liver as found in literature. Ann Intern Med 1954;40:111-4.  Back to cited text no. 14  [PUBMED]  
15.Auinger M, Irsigler K, Breiteneder S, Ulrich W. Normocalcemic hepatorenal sarcoidosis with crescentic glomerulonephritis. Nephrol Dial Transplant 1997;12:1474-7.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Longcope WT, Frieman DG. A study of sarcoidosis based on combined investigations of 160 patients including 30 autopsies from Johns Hopkins Hospital and Massachusetts General Hospital. Medicine 1952;31:132-40.  Back to cited text no. 16    
17.Shintaku M, Mase K, Ohtsuki H, et al. Generalized sarcoid like granuloma with systemic angeiitis, crescentic glomerulo­nephritis and pulmonary hemorrhage: report of an autopsy patients. Arch Pathol Lab Med 1989;113:1295-8.  Back to cited text no. 17  [PUBMED]  
18.Van Uum SH, Cooreman MP, Assmann KJ, Wetzels JF. A 58-year-old male with sarcoidosis complicated by focal crescentic glomerulonephrtis. Nephrol Dial Transplant 1997;12:2703-7.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]
19.Goldszer RC, Galvanek EG, Lazarus JM. Glomerulonephritis in a patient with sarcoidosis: Report of a patients and review of the literature. Arch Pathol Lab Med 1981;105:478-81.  Back to cited text no. 19  [PUBMED]  

Correspondence Address:
Hayet Kaaroud
Department of Internal Medicine, Boulevard 9 Avril 1938, 1006 BS Tunis
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