|Year : 2018 | Volume
| Issue : 4 | Page : 979-984
|Sarcoidosis with multiple organ involvement associated with necrotizing crescentic glomerulonephritis
Abdullah K Al-Hwiesh1, Ibrahiem Saeed Abdul-Rahman1, Amani Alhwiesh1, Nadia Al-Oudah2, Jumana Abdulwahab Alratroo2, Nahad Al-Oudah1, Fahd A Al-Muhanna1, Husain Alsharani3, Eman Fathi Ibrahim3, Ibrahim Al-Durayash4, Abdulhadi Jawad Al-Mubark4
1 Department of Internal Medicine, Division of Nephrology, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Al-Khobar, Saudi Arabia
2 Department of Pathology, Dammam Medical Complex, Dammam, Saudi Arabia
3 Department of Internal Medicine, Division of Nephrology, Security Forces Hospital, Dammam, Saudi Arabia
4 Department of Radiology, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Al-Khobar, Saudi Arabia
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|Date of Submission||20-Jul-2017|
|Date of Acceptance||08-Aug-2017|
|Date of Web Publication||28-Aug-2018|
| Abstract|| |
We report a case of a young Saudi male who presented with generalized body weakness and easy fatigability associated with fever, night sweating, loss of weight and appetite, and renal impairment. He was diagnosed as a case of sarcoidosis, and renal biopsy report was consistent with necrotizing crescentic glomerulonephritis (GN). Immunosuppressive medication was started to help halting the progression to renal failure and stabilize renal function. To the best of our knowledge, the association between sarcoidosis and crescentic GN has been reported in only few cases in literature.
|How to cite this article:|
Al-Hwiesh AK, Abdul-Rahman IS, Alhwiesh A, Al-Oudah N, Alratroo JA, Al-Oudah N, Al-Muhanna FA, Alsharani H, Ibrahim EF, Al-Durayash I, Al-Mubark AJ. Sarcoidosis with multiple organ involvement associated with necrotizing crescentic glomerulonephritis. Saudi J Kidney Dis Transpl 2018;29:979-84
|How to cite this URL:|
Al-Hwiesh AK, Abdul-Rahman IS, Alhwiesh A, Al-Oudah N, Alratroo JA, Al-Oudah N, Al-Muhanna FA, Alsharani H, Ibrahim EF, Al-Durayash I, Al-Mubark AJ. Sarcoidosis with multiple organ involvement associated with necrotizing crescentic glomerulonephritis. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Dec 11];29:979-84. Available from: http://www.sjkdt.org/text.asp?2018/29/4/979/239649
| Introduction|| |
Sarcoidosis is an illness of granulomatous inflammation with multiple organ involvement. Although lung involvement is the most common, renal involvement has also been associated with sarcoidosis. It was observed in approximately 4–22% of cases. Renal involvement may manifest as proteinuria, hematuria, hypercalciuria, and nephrocalcinosis. Granulomatous interstitial nephritis (GIN) is seen in 7–27%, while other glomerular diseases such as minimal change disease, membranous glome-rular nephritis, membranoproliferative glome-rulonephritis (GN), IgA nephropathy, and crescentic GN have also been reported.,,
Corticosteroids remain the cornerstone of renal therapy with good success rate, and prolonged therapy is often required to preserve renal function and delay the onset of renal failure.,,
We report on a young Saudi male who presented with generalized body weakness, fatigability and dry cough associated with fever, loss of weight, and renal impairment. He was found to have sarcoidosis, and renal biopsy revealed necrotizing crescentic GN and GIN. Immunosuppressive medication was started to prevent progression to renal failure and to stabilize renal function. This association between sarcoidosis and crescentic GN has been reported in very few cases in literature.
| Case Report|| |
Consent of the patient was obtained before reporting the case. The patient was a 31-year-old Saudi male, who presented to our hospital with a history of generalized body weakness and easy fatiga-bility associated with loss of weight and night sweating. He had lost about 8 kg over the last six months. He gave a history of exertional dyspnea, dry cough, and subjective fever. His condition worsened over the last six months to the limit that he could not perform his regular activity anymore, before his admission.
The patient also gave a history of generalized arthralgia of small joints of both upper and lower bilateral extremities. There was no history suggestive of autoimmune disease or family history of connective tissue disease. He denied any history of blood transfusion, illicit drug use or sexual contacts.
On physical examination: weight was 45 kg, height was 175 cm, the patient looked ill, thin, in respiratory distress, pale, and not jaundiced or cyanosed. Blood pressure was 125/75 mm Hg, respiratory rate was 28/min, heart rate was 100/min, and temperature was 38°C; there was no lymphadenopathy, and jugular venous pressure was not raised. Examination of the chest showed fine crepitations up to the middle zone bilaterally; there was hepatosplenomegaly, and there was no lower limb edema and peripheral pulses were intact, while examination of the central nervous system showed features of peripheral sensory neuropathy.
The serum creatinine was 3.5 mg/dL, blood urea nitrogen was 60 mg/dL, hemoglobin was 9 g/dL, white blood cell count was 10 x 10 L with predominant neutrophils, platelet count 150,000, erythrocyte sedimentation rate 120 in 1st h, serum sodium was 140 mmol/ L, potassium was 4 mmol/L, chloride 97 mmol/L, HCO3 was 25 mmol/L, calcium 12.2 mg/dL, phosphate was 4.5 mg/dL, parathormone 300, albumin was 3.6 g/dL, magnesium was 1.9 mg/dL, 1.25 dihydroxycholecalciferol 100 (1575) and 24-h urine calcium was 400 mg, angiotensin-converting enzyme (ACE) was 200 U/L (normal 16–68 U/L), fasting blood glucose was 110 mg/dL, liver enzyme alkaline phosphatase was 350 U/L (normal: 7–40) serum glutamate oxaloacetate transaminase was 90 (normal: 5–35) gamma glutamate transpepti-dase was 600 (normal: 2–85); the antinuclear antibody, anti-DNA, complement C3, C4 Ch50, rheumatoid factor and anti-neutrophil cytoplasmic antibodies (ANCAs) were all within normal limits. Hepatitis serology A, B, and C were negative and anti-human immunodeficiency virus antibody was negative, tuberculin test was negative and, serum and urine electrophoresis with immunofixation were normal.
Computer tomography (CT) of the chest and abdomen showed bilateral diffuse and homogenous micronodular pattern with per bronchial distribution with bilateral hilar lymphadeno-pathy and hepatosplenomegaly [Figure 1] and [Figure 2]. Bronchoscopy with lavage was negative for tuberculosis and malignant cells, and transbronchial biopsy showed multiple noncaseating granulomas compatible with sarcoidosis.
|Figure 1: Computerized tomography scan showing bilateral diffuse and homogenous defined micronodular pattern with per bronchial distribution with bilateral hilar lymphadenopathy.|
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Renal ultrasound showed normal-sized kidneys with bilateral nephrocalcinosis, renal biopsy showed severe noncaseating epithelioid granulomatous necrotizing interstitial nephritis, necrotizing vascular lesion and cellular crescent formation and intratubular calcinosis was occasionally noted [Figure 3], with mild-to-moderate tubular atrophy. Immunofluorescence studies were negative for immunoglobulin IgA, IgM, IgG, Kappa, lambda, C1q, C3, and electron microscopy revealed no immune complex deposits.
|Figure 3: Renal biopsy showing severe non-caseating epithelioid granulomatous necrotizing interstitial nephritis, necrotizing vascular lesions, and cellular crescent formation; intratubular calcinosis is occasionally noted.|
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Liver biopsy was performed due to infiltrative pattern and derangement of liver enzymes and showed granulomatous inflamma tion negative for tuberculosis and fungal infection [Figure 4].
Urine analysis showed active urine sediment and 24-h urine protein was 1.3 g. Pulmonary function tests were consistent with the restrictive pattern.
Echocardiogram was normal. Due to multiple organ involvement and hypercalcemia, the patient was started on pulse methylpredni-solone and azathioprine 150 mg daily. Within four weeks, the patient showed a dramatic response with improvement of CT chest findings and stabilization of renal function along with improvement in general well-being and weight gain. He was maintained on azathioprine and a small dose of prednisolone for two years. After four years follow-up, the serum creatinine was 1.8 mg/dL, and 24-h urine protein was 400 mg. The ACE, serum calcium, and liver enzymes were normal on only a small dose of prednisolone.
| Discussion|| |
Sarcoidosis mainly affects only the pulmonary system in about 90% of the cases presenting with mostly hilar lymphadenopathy but also, dry cough, exertional dyspnea, pulmonary hypertension, and obstructive and restrictive airway disease. Other major organ systems disturbed include the skin, the eye, the heart, and the nervous system with approximately 25-30% involvement. Little is known about the prevalence of renal sarcoidosis in literature.
GIN is a rare histologic diagnosis that is present in between 0.5 and 0.9% of native renal biopsies and 0.6% of renal transplant biopsies. There are many causes of GIN including sarcoidosis, Sjogren's syndrome, crystal deposits, infections, paraproteinemia, and Wegener's granulomatosis (WG) and is also seen in an idiopathic form.,,
Drugs related include anticonvulsants, antibiotics, nonsteroidal anti-inflammatory drugs, allopurinol, and diuretics. Mycobacteria and fungi are the main infective causes and seem to be the main causative factor in cases of renal transplants. Although autopsy series have demonstrated that non-caseating granulo-matous disease are present within the renal interstitium in 15–30% of patient with sarcoidosis, it is unusual for these pathological abnormalities to result in clinically apparent renal dysfunction., Eighteen patients with GIN were identified in Glasgow case series over a 15-year period. Five cases were associated with sarcoidosis, two were associated with tubulointerstitial nephritis and uveitis, two were associated with medication, and nine were idiopathic. Patients presented with advanced renal failure (median estimated creatinine clearance 21 mL/min) and minimal proteinuria (urine albumin-to-creatinine ratio 9.9 mg/mmol). Sixteen patients were treated with prednisolone for a mean of 25 months while six patients relapsed with reduction in prednisolone dosage, and four patients required steroid-sparing agents. During a mean follow-up of 45 months, renal functions improved or stabilized in 17 patients; the rate of improvement in renal function was most marked in the 1st year after diagnosis with a gain in function of 1.9 mL/min per month. The median estimated creatinine clearance at final visit was 56 mL/min.
Despite the granulomatous inflammation that characterizes sarcoidosis, deranged calcium homeostasis has a greater effect on the kidneys than the invasive granulomas themselves. Activated pulmonary macrophages express 1-a hydroxylase. Extrarenal production of 1-a hydroxylase inappropriately increases calcitriol levels, thereby increasing serum calcium and decreasing PTH. Unlike its renal equivalent, the granulomatous 1-a hydroxylase is immune from the normal negative feed back mechanisms of hypercalcemia and is therefore unregulated causing disturbed calcium homeo-stasis. This not only causes hypercalcemia, hypercalciuria and possibly subsequent nephro-lithiasis and nephrocalcinosis, which itself is the most common cause of progressive renal failure. The clinical consequences of each imbalance range from trivial presentation to overt pathology including dehydration, renal colic, and end-stage renal disease (ESRD). Hypercalcemia may cause decreased glomerular filtration rate (GFR) by causing vasoconstriction of the afferent arterioles and thereby decreasing renal blood flow. In addition, it may cause tubular necrosis, tubulo-interstitial nongranulomatous inflammation with calcium deposits ultimately causing nephrocalcinosis and chronic kidney disease similar to our patient. Hypercalciuria, which is three times more common than hypercalcemia, predisposes patients to calcium oxalate nephro-lithiasis, which may ultimately lead to obstruction or chronic pyelonephritis., Renovascular complications as well as obstructive nephropathy may also occur.
Glomerular involvement in sarcoidosis is not very common. The spectrum of commonly reported glomerular diseases includes focal and segmental glomerulosclerosis, membranous GN, mesangioproliferative GN, mesangiocapillary GN, IgA nephropathy, and crescentic GN. The exact mechanisms of glomerular disease in sarcoidosis are not known. Crescentic GN has also been infrequently reported in patients with sarcoidosis-associated vasculitis.
Crescentic or rapidly progressive GN (RPGN) represents a nephrological emergency. It may be commonly linked to ANCA vasculitis, antiglomerular basement membrane disease, or complement-mediated cases of lupus nephritis, cryoglobulinemia, IgA nephropathy, and post-infectious GN. The major clinical characteristics of the disease may include a marked decline in renal function along with active urinary sediment. Renal pathology demonstrates the presence of cellular crescents at the beginning of the disease, which frequently progress to fibrocellular crescents. If these patients are not promptly treated with immuno-suppressive therapy, RPGN will lead to irreversible damage and ESRD. Auinger et al described a patient similar to our patient who presented with RPGN and hepatosplenomegaly with no prior diagnosis of sarcoidosis whose renal biopsy showed crescentic GN. Diagnosis of sarcoidosis was made with raised ACE levels and both liver and kidney biopsies showing interstitial noncaseating granulomas.
Our patient was started on high-dose steroids with which renal function improved. Subsequently, the patient developed antimyeloper-oxidase antibodies. In contrast, Ahuja et al reported a patient with crescentic GN in the setting of WG. The patient responded well to long-term oral cyclophosphamide treatment. Subsequently, the patient developed biopsy-confirmed pulmonary sarcoidosis months later.
The usual cause of ESRD in sarcoidosis requiring renal replacement therapy is usually hypercalcemic nephropathy rather than GIN or a glomerular disease. The outcome of renal transplantation in patients with sarcoidosis has been described in a French study aimed to describe a multicenter experience with kidney transplantation in patients with sarcoidosis. In 18 patients who underwent renal transplantation, renal disease was attributable to biopsy-proven renal sarcoid in 10 out of the 18 patients while eight patients were attributed to other causes. Mean age at transplantation was 43.5 ± 11 years. Seventeen out of 18 patients had a deceased donor transplant. Mean donor age was 36.5 ± 15 years. At the end of the 42 months follow-up period, the patient and death-censored graft survival was 94.4% and mean GFR was 60 mL/min per 1.73 m2. Recurrence of sarcoidosis after renal transplantation was observed in five patients (27%).
This study showed that renal transplant can be performed safely in transplant patients with sarcoidosis, but recurrences do occur and affect overall graft outcome.
| Acknowledgment|| |
The authors wish to express their sincere thanks and appreciation to the nursing staff of three-dimensional male medical ward at the King Fahad Hospital of the University, Alkhobar, KSA, for their valuable support during hospitalization of the patient. In addition, the authors would like to thank the staff members of histopathology department of the same hospital for their assistance.
Conflict of interest: None declared.
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Prof. Abdullah K Al-Hwiesh
Department of Nephrology, King Fahd University Hospital, Alkhobar
[Figure 1], [Figure 2], [Figure 3], [Figure 4]