| Abstract|| |
Sarcoidosis is one of the granulomatus disorders affecting many organ systems of the body. Renal impairment in sarcoidosis is rare and occurs usually as a result of long standing hypercalcemia or hypercalciuria with nephrocalcinosis or renal stones. Sarcoid glomerulopathy and tubulo-interstitial granulomatus involvement have been described. We report two cases of sarcoidosis, the first with interstitial nephritis and anterior uveitis without evidence of granuloma. The patient was normocalcemic and normocalciuric. The second case presented with nephritic range proteinuria and severe renal insufficiency with a history of recurrent parotid swelling seven years before diagnosis. Renal biopsy showed non-caseating granulomas in the tubulo-interstitial region. Both patients showed good response to steroid therapy, however, there is still residual renal insufficiency six months after therapy. In conclusion, renal sarcoidosis although a rare presentation, should be considered in the presence of extra-renal manifestation of sarcoidosis as it is amenable to treatment.
Keywords: Sarcoidosis, Renal failure, Nephrocalcinosis, Glomerulopathy.
|How to cite this article:|
Mitwalli AH, Abu-Aisha H, Al-Wakeel J, Memon NA, Al-Mobeireek A, Huraib SO. Sarcoidosis with Partial Reversibility of Renal Failure: Two Case Reports with Review of Literature. Saudi J Kidney Dis Transpl 1998;9:451-6
|How to cite this URL:|
Mitwalli AH, Abu-Aisha H, Al-Wakeel J, Memon NA, Al-Mobeireek A, Huraib SO. Sarcoidosis with Partial Reversibility of Renal Failure: Two Case Reports with Review of Literature. Saudi J Kidney Dis Transpl [serial online] 1998 [cited 2020 Jun 5];9:451-6. Available from: http://www.sjkdt.org/text.asp?1998/9/4/451/39105
| Introduction|| |
Sacroidosis is a chronic multi-system disorder of unknown etiology. It is characterized by accumulation of Tlymphocytes and mononuclear phagocyte formation of non-caseating granulomas and subsequent derangement of tissue architecture. 
Prevalence of sarcoidosis in USA and Europe is 40 cases per 100,000. The disease is rare in Canada, Japan and the Middle East.  Renal involvement in sarcoidosis is even rarer and occurs only in about 10% of cases.
Sarcoidosis can cause renal functional or structural damage in a number ways: a) Tubulo-interstitial granulomatus nephritis, sarcoid glomerulopathy, b) long standing hypercalcemia or hypercalciuria with nephrocalcinosis and c) secondary to hypergamaglobulinimia. Whereas the effects of hypercalcemia on the kidney are not uncommon in sarcoidosis, direct granulomatus involvement or interstitial sarcoid inflammations are unusual. 
Reviewing the literature from Saudi Arabia about sarcoidosis, we found only a small series reported describing mainly the pulmonary and ophthalmic involvement with sarcoid. 
We report two Saudi patients, one presenting with normocalcemic interstitial nephritis and anterior uveitis and the other with parotid swelling seven years before renal involvement and could only be diagnosed 10 years after initial symptoms. Renal biopsy showed characteristic noncaseating granulomatous formation. Both cases and pertinent review of literature are presented.
| Case 1|| |
A twenty-nine year old Saudi female was referred to our unit from King Faisal Eye Specialist Hospital (KFESH) Riyadh with diagnosis of anterior uveitis of undetermined etiology. She was worked up earlier for anemia at another hospital in Saudi Arabia, and was told that she has chronic renal failure (CRF). She was referred for further work-up and management.
The patient presented with dizziness, vomiting, anorexia and fatigue of four months duration and had lost eight kg of weight. She had loin pain and burning micturation two years earlier during her last pregnancy. This was treated with antibiotics. The pregnancy ended with normal delivery.
She denied history of joint pains, skin rashes, mouth ulcers or deafness and had no history of nephrotoxic drug usage.
She was not diabetic or hypertensive and had no family history of similar illness or renal disease.
On physical examination the patient looked pale, blood pressure 110/70 mmHg. Ophthalmic examination revealed anterior uveitis. The rest of the systemic examination was unremarkable.
She was admitted with a working diagnosis of interstitial nephritis (chronic pyelonephritis) for further investigations.
Investigations revealed the following: [Table - 1] - Hemoglobin was 77 gm/L. Urinalysis showed WBC 40/HPF and RBC 20/ HPF and no protein and sugar present, urine culture revealed no growth. Blood urea 22 mmol/L, serum creatinine 605 umol/L, Na 136 mmol/L, K 3.8 mmol/L, Cl 101 mmol/L, HCO3 11 mmol/L, serum calcium, PO4 and alkaline phosphatase were normal. Liver enzymes (LFT) were normal. Twenty-four hours urine protein was 0.6 gm. VDRL, HbsAg and HCV were negative. ANA, Anti DNA, C3, C4, were normal. Serum immuno-electrophoresis and thyroid function tests were normal. Sputum and urine for acid fast bacilli (AFB) stain were negative. Ultrasound of the kidneys showed increased parenchymal echogenicity. Right kidney was 10.1 cm and left 11.4 cm in length with no evidence of obstruction. DTPA and DMSA renograms showed poor cortical uptake consistent with chronic renal failure. Chest X-ray and ECG were normal.
The working diagnosis was anterior uveitis and renal failure. The etiology for this association includes; ankylosing spondylitis, Reiters Syndrome, juvenile chronic arthritis (ANA positive pauciarticular), inflammatory bowel syndrome, syphillis, Sjoren's syndrome and sarcoidosis.
Gallium 67 showed increased uptake in the lacrimal glands, parotids, lungs and kidneys suggestive of active sarcoidosis.
Computerized tomography of the chest showed minimal peripheral changes. The level of serum angiotensin converting enzymes was 44 u/1 (N=12-42 U/L). Trans-bronchial biopsy did not show evidence of granulomata. Renal biopsy showed interstitial infiltrate compatible with the clinical diagnosis of renal sarcoidosis but granulomata were not seen [Figure - 1].
The patient was placed on prednisolone 40 mg/day for four weeks, tapered to maintenance dose of 20 mg/day and responded very well. Her constitutional symptoms got better. She gained weight. Four months after steroids therapy her blood urea stabilized at 6.6 mmol/L and serum creatinine at 181 umol/L.
| Case 2|| |
Thirty-three year old Saudi male was admitted with a history of generalized fatigue and tiredness. He has been followed up in the nephrology clinic for three years for hypertension, proteinuria and mild degree of renal insufficiency. He denied any urinary symptoms. There was no history of joint pains, skin rash, sore throat, deafness or use of nephrotoxic drugs. He has no family history of renal disease and is not diabetic.
His past history revealed that ten years ago he presented to the surgical clinic with a history of parotid swelling and fever. The presumptive diagnosis was mumps and the swelling regressed. He was re-admitted two years. later with recurrence of parotid swelling, silogram was done at that time and was found to be normal. The patient was reassured and sent home although Gallium 67 scan was done which was reported to have increased uptake and raised the possibility of Sjoren's syndrome. However, this was not pursued further. Four years later the patient was readmitted with bullous skin eruptions, thought to be pemphigoid and skin biopsy was in keeping with the diagnosis. The patient was put on steroids to which he showed good response. At that time he had mild elevation of blood urea to 8.9 mmol (thought to be due to steroids) as the serum creatinine was normal. The patient was lost to follow-up for two years and later presented to the clinic with hypertension and renal insufficiency with serum creatinine of 400 µmol/L and 24 hours protein of 500 mg on dipstick. The hypertension was adequately controlled on Captropril. Apart from mild pallor, physical examination was within normal limits.
Investigations revealed the following: [Table - 1] hemoglobin 11.5 gin/L, urinalysis showed urinary protein 3+ and benign sediment, 24 hrs urine protein 5 gms, blood urea 22 mmol/L, serum creatinine 526 µmol/L, LFT were normal, serum calcium and 24 hrs urinary calcium were normal. C 3 , C 4 , ANA, anti DNA were normal, HbsAg and HCV were negative and Brucella More Details screens were negative.
Chest X-ray and ECG were normal. Renal ultrasound revealed increased parenchymal echogenecity, right kidney was 10.1 cms and left kidney were 9.6 cms. DTPA and DMSA renograms were consistent with chronic renal failure. Acid fast bacilli stain for both sputum and urine were negative.
As this patient had renal insufficiency and history of parotid swelling and increased Gallium uptake by the parotid gland, the possibility of Sjoren's syndrome was considered. However, as there was no history of joint pains, differential diagnosis of sarcoidosis was considered and Gallium 67 was repeated. It showed increased uptake in lacrimal glands, parotids, lungs and kidneys, consistent with active sarcoidosis.
Renal biopsy was performed which showed non-caseating granulomas without evidence of vasculitis or evidence of AFB, a diagnosis consistent with sarcoidosis [Figure - 2]. The patient was put on prednisolone 60 mg/day for eight weeks, tapered to maintenance dose of 20 mg/day to which he responded well and a month later his serum creatinine became 350 µmol/I
| Discussion|| |
Sarcoidosis is a chronic multi-system disease of unknown etiology characterized by the formation of non-caseating epitheloid cell granulomas and accumulation of T-Lymphocytes and monoclear phagocytes and derangement of tissue architecture and function.  Sarcoidosis most commonly affects young adults, presenting frequently with bilateral hilar lymphadenopathy, pulmonary infiltrates, skin and eye lesions  . Clinical renal involvement occurs in less than 10% of case. Destruction of renal function and structure occurs due to one of the following mechanisms:
a) Granulomatus involvement of tubulointerstitial region,
b) long standing hypercalcemia or hypercalciuria and nephrocalcinosis,
d) glomerular involvement.
Diffuse proliferative, focal segmental (FGS), membranous and rapidly progressive glomerulonephritis have all been described but are rare. ,,
Our first patient had anterior uveitis and severe degree of renal insufficiency. Sarcoidosis presenting as such is usually associated with hypercalcemia  . In our case, however, the serum calcium was normal, and so was the urinary calcium. Except for eyes and kidneys no other organ system was involved. Review of the literature showed that sarcoidosis can present with an elevated plasma creatinine concentration with no or only minimal extra renal manifestation  . Normocalcemic interstitial nephritis is well documented by others , Yamaguchi et al  , reported a case of 14 year old female who had acute tubulointerstitial nephritis (AIN) associated with bilateral diffuse uveitis. She was admitted for evaluation of "proteinuria", following general fatigue and weight loss of two weeks duration. Her laboratory investigations showed mild anemia, hypergammaglobulinemia, and mild proteinuria and reduced GFR with increased excretion of beta 2-microglobulin. Renal biopsy showed AIN. Clinical investigations could not reveal any specific cause such as bacterial and viral infections, drugs or systemic diseases. Four months after the onset of nephritis she suffered from bilateral diffuse uveitis. Therefore, the diagnosis of the acute tubulointerstitial nephritis and uveitis syndrome (TINU) could be confirmed. In this patient uveitis frequently relapsed inspite of systemic administration of prednisolone and it took two years until uveitis was cured whereas AIN subsided spontaneously prior to the specific treatment. In the above case characteristic findings of granulomatus uveitis was closely similar to those of sarcoidosis. In this respect, the improvement of immune processes, specially cell mediated was suggested as the possible pathogenesis in this case. Shah et al  also reported a 43year old white man who presented with history of linear interference and blurring of vision of his left eye preceded by black spots. Diagnosis of uveitis was made involving the left eye. The BP was high 180/110 mmHg and there was renal involvement, with serum creatinine of 414 µmol/L. Renal biopsy showed granulomatus interstitial nephritis with little glomerular necrosis. Initial diagnosis of Wegner's granulomatosis involving lacrimal gland, retina and kidney was made. The patient made good recovery with steroids and immunosuppressive therapy and serum creatinine fell to 160 µmol/L. Within three months the eye involvement resolved totally. The case was reviewed again and it was appreciated that the hilar lymphadenopathy observed previously might have represented sarcoidosis. The renal histology was reviewed also and was considered more typical of sarcoidosis than Wegner's granulomatosis. The authors pointed out that the unusual combination of systemic features may not be widely recognized and should not be confused with Wegner's granulomatosis and polyarteritis.
Cruzado et al reported interstitial nephritis in sarcoidosis but there were extra renal manifestations present simultaneously.  None of the two patients had multi system organ involvement.
Our second patient had parotid swelling years before he presented with renal insufficiency and hypertension that had been well described by others  . No other organ system was involved. The parotid swelling was initially thought to be due to Sjoren's syndrome. As arthritis is a prominent feature of Sjoren's syndrome in its absence, other possibilities such as sarcoidosis should be suspected. The presence of parotid and lacrimal gland enlargement is a known association with sarcoidosis (Mikulicz's syndrome).  The kidney biopsy showed typical findings of non-caseating granulomata that is seen in sarcoidosis  .
Neither of our two patients had documented renal calculi which is reported to occur in 10% of patients with chronic sarcoidosis. They also did not show evidence of glomerulonephritis, which can occur in some cases of sarcoidosis. 
Both patients showed good but incomplete response to steroid therapy and both required long term follow up on maintenance steroid therapy. 
In conclusion, sarcoidosis although a rare disease in Saudi Arabia and rarely involves the kidneys, should be considered by the nephrologist in the appropriate clinical setting.
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Ahmed H Mitwalli
Department of Medicine, King Khalid University Hospital, Riyadh
[Figure - 1], [Figure - 2]
[Table - 1]