Isolated sarcoid granulomatous interstitial nephritis: review of five cases at one center

AIMS: To identify any clinical or biochemical parameters which determine prognostic outcome in isolated sarcoid granulomatous interstitial nephritis presenting with renal failure. METHODS: A review of five cases of renal failure due to isolated sarcoid granulomatous interstitial nephritis, which presented to Hope Hospital over the 7-year period 1994 to 2000. Follow-up averaged 35 months with a range of 11 to 73 months. RESULTS: Only one patient had an elevated serum ACE at presentation, reflecting the suboptimal sensitivity of this test as a marker in sarcoidosis and the limited extent of disease in these patients. Four of the five cases had a marked improvement in creatinine clearance within 10 days of starting oral prednisolone. Two patients required acute hemodialysis on presentation. Their renal failure responded to treatment with steroids, enabling withdrawal of dialysis within 10 days. All patients remained dialysis-independent although serum creatinine levels rose during follow-up. One patient experienced a relapse that responded to an increased dose of steroid. CONCLUSIONS: Serum ACE is not reliable in the diagnosis of renal failure due to sarcoid interstitial nephritis and the diagnosis can only be made on renal biopsy. First-line treatment with oral prednisolone results in a rapid improvement in creatinine clearance although prolonged treatment may be needed to prevent a relapse.     

Seven cases of granulomatous interstitial nephritis in the absence of extrarenal sarcoid.

BACKGROUND: Renal disease in sarcoidosis may occur due to granulomatous interstitial nephritis. However, granulomatous interstitial nephritis in the absence of features of extrarenal sarcoid, or other causes, has been reported very rarely. In this report we describe seven such patients. METHODS: Since 1995, we have identified a number of patients with biopsy-proven granulomatous interstitial nephritis. Patients were excluded if they had (i) evidence of extrarenal sarcoid, (ii) infections that may have contributed to pathogenesis or (iii) an obvious drug-related aetiology. RESULTS: Seven patients were identified, of whom five were male and two female, with a median age of 69. Median calculated creatinine clearance at presentation was 14 ml/min. Two had raised serum calcium at presentation and three had a raised serum angiotensin-converting enzyme. All patients were treated with steroids and five out of seven had an improvement in their renal function. Two patients progressed to end-stage renal failure despite treatment with steroids. CONCLUSIONS: Idiopathic granulomatous interstitial nephritis may represent a renal-limited form of sarcoid. It may be associated with hypercalcaemia and a raised serum angiotensin-converting enzyme and usually responds to treatment with corticosteroids.     

Delayed graft function and cotrimoxazole

Acute interstitial nephritis is an infrequent cause of early allograft dysfunction. Prophylactic trimethoprim sulfamethoxazole (cotrimoxazole) is frequently prescribed early in the course of kidney transplantation. Herein we have reported a case of delayed graft function associated with eosinophilia in which the renal biopsy showed interstitial mononuclear infiltrates with abundant eosinophils. An initial methylprednisolone course failed to lower the serum creatinine, but renal function and eosinophilia persistently improved following cotrimoxazole withdrawal and a second course of steroids. Cotrimoxazole acute interstitial nephritis is an infrequent but treatable cause of kidney allograft dysfunction, which should be included in the differential diagnosis of delayed renal allograft function.     

Interstitial nephritis induced by mesalazine

This report concerns the first case in Japan of interstitial nephritis induced by mesalazine, a new therapeutic agent for inflammatory bowel disease, such as ulcerative colitis. Twenty-two cases have already been reported in other countries. The patient, a 27-year-old woman, was treated with mesalazine for her ulcerative colitis at another hospital. At the beginning of her treatment, her serum creatinine level was within the normal range. After 12 months, this level increased up to 5.7 mg/dl. She was then referred to our hospital for renal investigation and therapy. A renal biopsy revealed that severe tubulo-interstitial nephritis had occurred. Her mesalazine treatment was withdrawn and prednisolone was administered. Her serum creatinine level decreased gradually. However, this level remained at about 2.8 mg/dl and stabilized at that level. She was then discharged from the hospital. Glomeruli appeared to have minor glomerular abnormalities except for one globally sclerosed glomerulus as observed by light microscopy. However, IgM and C3 deposition on glomeruli were also observed. Glomerular lesions were suspected from these histological findings. A similar case that showed IgM. C3 depositions in glomeruli has previously been reported. The possibility of glomerular lesions being induced by mesalazine should be further researched. From the summary of reported cases, a delay of diagnosis of interstitial nephritis induced by mesalazine has resulted in permanent irreversible renal failure. Intensive monitoring of renal function is required when a patient is treated with mesalazine.     

Acute interstitial nephritis associated with the use of mesalazine in inflammatory bowel disease

BACKGROUND: In the last 10 years several reports have linked oral 5-aminosalicylic acid (5-ASA) therapy to acute and chronic tubulointerstitial nephritis, but to our knowledge only 2 patients have been reported with terminal end-stage renal disease due to mesalazine (5-ASA). After 1 year of treatment with 5-ASA annual monitoring of serum creatinine is recommended. RESULTS: We report the development of end-stage renal disease in a patient 10 months after the last assessment of serum creatinine, which was normal at 71 micromol/l. CONCLUSION: Because of this dangerous side effect, we would like to recommend 6-monthly assessment of renal function.     

Reversible renal failure due to isolated renal sarcoidosis

Renal impairment in sarcoidosis is usually due to hypercalcaemia and nephrocalcinosis but can also be caused by granulomatous nephritis or interstitial nephritis without sarcoid granulomata. A variety of types of glomerulonephritis have also been described in sarcoidosis but these rarely cause impaired renal function. Renal failure as an isolated manifestation of sarcoidosis is uncommon. A 66-year-old woman presented with a 1-year history of lethargy, polyuria and nocturia. Clinical examination was unremarkable and she had impaired renal function (urea 18 mmol/l (108 mg%) and creatinine 380 mumol/l (4.3 mg%)). As her kidneys were normal in size, she underwent renal biopsy, which revealed granulomatous interstitial nephritis. Reevaluation showed no other evidence of sarcoidosis and she had impaired urinary acidification and concentrating capacities. Therapy with corticosteroids produced a marked improvement in symptoms and renal function. This case confirms the view that granulomatous sarcoid nephritis is steroid sensitive and that full recovery can be expected provided interstitial fibrosis and scarring do not occur.     

Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis

The role of steroid treatment in drug-induced acute interstitial nephritis (DI-AIN) is controversial. We performed a multicenter retrospective study to determine the influence of steroids in 61 patients with biopsy-proven DI-AIN, 52 of whom were treated with steroids. The responsible drugs were antibiotics (56%), non-steroidal anti-inflammatory drugs (37%) or other drugs. The final serum creatinine was significantly lower in treated patients while almost half of untreated patients remained on chronic dialysis. Among treated patients, over half showed a complete recovery of baseline renal function, whereas the rest remained in renal failure. There were no significant initial differences between these two subgroups in terms of duration or dosage of steroids. After withdrawal of the presumed causative drug, we found that when steroid treatment was delayed (by an average of 34 days) renal function did not return to baseline levels compared to those who received steroid treatment within the first 2 weeks after withdrawal of the offending agent. We found a significant correlation between the delay in steroid treatment and the final serum creatinine. Renal biopsies, including three patients who underwent a second biopsy, showed a progression of interstitial fibrosis related to the delay in steroid treatment. Our study shows that steroids should be started promptly after diagnosis of DI-AIN to avoid subsequent interstitial fibrosis and an incomplete recovery of renal function.     

Chronic interstitial nephritis due to 5-aminosalicylic acid.

Nephrotoxicity has recently been reported with the use of 5-aminosalicylic acid (5-ASA) which has structural similarities to phenacetin and aspirin. The present paper describes 2 cases of interstitial nephritis and 1 case of end-stage failure associated with 5-ASA treatment. The first patient presented with severe renal failure which was partially reversed with 5-ASA discontinuation and steroid therapy. The second had severe renal failure (serum creatinine 469 mmol/l) but renal function stabilized with 5-ASA withdrawal. The third patient had end-stage renal failure and underwent hemodialysis and a successful kidney transplant.     

Two cases of interstitial nephritis with primary Sjögren's syndrome successfully treated by steroid therapy

We have experienced two cases of interstitial nephritis with Sj?gren's syndrome successfully treated by steroid therapy. Case 1. A 50-year-old woman was admitted because of rash and arthralgia of the limb. Although her renal function was normal, serum IgG was extremely high and gallium-67 scintigrams indicated abnormal uptake in both kidneys with swelling on CT scans. Renal biopsy specimens showed a patchy dense interstitial infiltration of lymphocytes, monocytes and partly plasma cells with tubular cell atrophy. To suppress an excessive immune reaction, oral prednisolone was administrated at a dose of 30 mg/day. Six weeks after inception of the therapy, re-biopsy specimens showed a decrease in interstitial infiltration, particularly plasma cells, and interstitial fibrosis did not progress. After 8 weeks, the serum IgG level was normalized. Case 2. A 57-year-old woman was found to have renal involvement(serum creatinine level: 2.2 mg/dl) and anemia. Clinical findings suggested primary Sj?gren's syndrome with renal tubular acidosis. Renal biopsy specimens showed a moderate to severe interstitial infiltration of inflammatory cells. After inception of steroid therapy(prednisolone 40 mg/day), renal involvement and renal anemia gradually improved. The renal function has been kept stable(serum creatinine level: 1.5 mg/dl) for 9 years by low-dose steroid therapy. These two cases suggest that steroid therapy plays two important roles: controlling of the acute immune reaction that causes renal fibrosis to progress in case 1, and long-term preservation of the renal function by the continuous use of low-doses in case 2.     

COX-2 inhibitors and acute interstitial nephritis: case report and review of the literature

We report a case of biopsy-proven acute interstitial nephritis (AIN) in a 50-year-old diabetic woman, who had been treated with celecoxib for 4 weeks before presentation. She presented with clinical findings of renal proximal tubulopathy, aseptic leukocyturia and acute renal failure. A kidney biopsy specimen showed AIN with intense tubuli and eosinophilic infiltrate in the interstitium. She recovered normal renal function two weeks after cessation of celecoxib and use of a corticosteroid. A review of the literature yielded eight cases of COX-2 inhibitor-associated AIN with a biopsy-proven diagnosis. Among the reported cases, AIN was diagnosed after an average of 8.3 months of therapy (SD 12 months, range 3 days - 3 years) with 25 mg rofecoxib or 200 mg celecoxib daily. Common symptoms included asthenia, anorexia, nausea and vomiting. The classic triad of fever, rash and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, eosinophilia. Renal failure was common at the time of diagnosis. Mean serum creatinine levels were 0.86 +/- 0.11 mg/dl, 5.66 +/- 3.50 mg/dl and 1.15 +/- 0.24 before treatment, at time of diagnosis and 1 - 2 months after COX-2 inhibitor withdrawal, respectively. Three patients required emergency hemodialysis. After cessation of COX-2 inhibitor treatment, patients recovered completely with a normalized serum creatinine level after one to two months. Management consisted of withdrawal of the COX-2 inhibitor drug and in four patients, corticosteroid therapy was well-tolerated and may have been beneficial.     

CEPHOTAXIME-ASSOCIATED ALLERGIC INTERSTITIAL NEPHRITIS AND MPO-ANCA POSITIVE VASCULITIS

We report a case of reversible acute renal failure after cephotaxime treatment in a patient affected by non-Hodgkin lymphoma. Renal biopsy showed necrotizing vasculitis associated with eosinophil-rich interstitial inflammatory infiltrates and patchy infiltrates of CD20+ lymphoid cells. High serum p-ANCA titers were also detected. Drug withdrawal was closely related with recovery of renal function and disappearance of ANCA. Acute renal failure therefore represented a consequence of ANCA-mediated renal vasculitis and acute interstitial nephritis related to cephotaxime treatment.     

Cephotaxime-associated allergic interstitial nephritis and MPO-ANCA positive vasculitis

We report a case of reversible acute renal failure after cefotaxime treatment in a patient affected by non-Hodgkin lymphoma. Renal biopsy showed necrotizing vasculitis associated with eosinophil-rich interstitial inflammatory infiltrates and patchy infiltrates of CD20+ lymphoid cells. High serum p-ANCA titers were also detected. Drug withdrawal was closely related with recovery of renal function and disappearance of ANCA. Acute renal failure therefore represented a consequence of ANCA-mediated renal vasculitis and acute interstitial nephritis related to cefotaxime treatment.     

A case report of BK virus nephropathy after an ABO-incompatible living kidney transplantation

We present a case of 29-year-old female who underwent an ABO-incompatible living kidney transplantation from her father. The serum creatinine (s-Cr) level of this patient was stabilized about 1.1-1.2 mg/dl during the first 3 months after the transplantation. Thereafter, the function of allograft was deteriorated gradually. A biopsy performed on post-transplant day (PTD) 520 to evaluate a rise in creatinine revealed an interstitial nephritis and chronic renal allograft nephropathy. The renal function worsened persistently, although we increased the dosage of immunosuppressant subsequently. The following biopsy performed on PTD 630 showed a suspicion of BK virus nephropathy, with a mass of tubular epithelial nuclear inclusions and an interstitial nephritis. The diagnosis of BK virus nephropathy was confirmed on the immunohistochemistry staining using anti-SV40 antibody and PCR analysis. Despite reducing the immunosuppressants, the function of the allograft worsened progressively and was lost on PTD 912.     

A case of granulomatous interstitial nephritis presented reversible renal failure treated with the steroid therapy: repeated renal biopsy case]

This report describes clinical and histopathological findings of a case of a 43-year-old male with granulomatous interstitial nephritis. The patient developed renal failure following renal insufficiency of 4 months duration. The patient presented with lethargy and nocturia. The first renal biopsy revealed granulomatous interstitial nephritis. There was no apparent evidence of a systemic granulomatous disease or drug hypersensitivity. Therapy with reducing regime of prednisolone produced a marked improvement in symptoms and renal function. Relapse occurred 3 months later in association with early discontinuation of the corticosteroid therapy. Ga-scintigraphy demonstrated an abnormal accumulation of gallium in both kidneys. The second renal biopsy did not show the obvious improvement. With the re-administration of the corticosteroid therapy, renal function rapidly improved again. Twelve months after the re-administration of the steroid therapy, Ga-scintigraphy showed no renal uptake. Corticosteroid therapy yielded a favorable outcome for renal function. The third renal biopsy showed disappearance of the granulomas lesion. Re-administration of the corticosteroid therapy continued for 22 months and the patient has not yet relapsed 9 months after the withdrawal of the steroid therapy.     

Renal papillary necrosis induced by naproxen

A 17-year-old healthy girl was admitted to our hospital with diffuse abdominal pain and decreased oral intake of about 11 days duration. About a week prior to admission, she had taken naproxen, 250 mg four times a day for 4 days. Physical examination was normal except for diffuse abdominal tenderness on deep palpation. Investigations revealed high serum BUN (42 mg/dl) and creatinine (4.0 mg/dl). Serum electrolytes and complement (C3, C4) levels and urinalysis were normal. Antinuclear-antibody and anti-dsDNA were negative. Kidney biopsy revealed renal papillary necrosis, acute tubular necrosis, and focal interstitial nephritis. A diagnosis of nonoliguric acute renal failure due to naproxen nephrotoxicity was made. She received intravenous hydration, and oral steroids, which was gradually discontinued in 3 months. A follow-up at 4 months revealed normal renal function with a serum creatinine of 1.1 mg/dl, BUN 7 mg/dl, and normal urinalysis. The report highlights a need for caution while using naproxen or any other nonsteroidal anti-inflammatory drugs, even for a short duration.     

IgA nephritis: on the importance of morphological and clinical parameters in the long-term prognosis of 239 patients

This study is concerned with the correlation between tubulointerstitial changes (interstitial fibrosis, acute renal failure, and interstitial fibrosis with acute renal failure), glomerular changes (focal and segmental lesions, hyperperfusion lesions), vascular changes, clinical data at the time of biopsy (serum creatinine concentration, creatinine clearance, hematuria, proteinuria, and hypertension) and first symptoms (hematuria, proteinuria and hypertension) and the kidney survival rate in 239 patients with IgA nephritis without nephrotic syndrome. The morphological and clinical parameters were subjected to multivariate analysis in order to examine their significance with regard to the prognosis. The interstitial fibrosis was proven to be the most important morphological parameter, and the most important clinical parameters were the serum creatinine concentration and the creatinine clearance.     

Short-term prognosis of severe proliferative lupus nephritis

The prognosis of systemic lupus erythematosus (SLE) is considerably worse when accompanied by renal involvement. In order to study the outcome within a year of histologic diagnosis of severe lupus nephritis, we obtained data on 25 patients from nine participating centers. All these patients fulfilled clearly defined histologic criteria of severe lupus nephritis, thus enabling us to evaluate a homogeneous group of patients. During a mean follow-up period of 9.4 months, there appeared to be an equal probability that the renal function would improve, remain stable, or worsen as assessed by changes in serum creatinine concentration. One patient died and another patient reached end-stage renal disease (ESRD), a combined crude mortality plus ESRD rate of 8% for 9.4 months. As both these patients had serum creatinine values of less than 2 mg/dL at the time of diagnosis of severe lupus nephritis, it appears that normal or mildly impaired renal function at the time of diagnosis does not ensure benign outcome. These features should be considered when new studies on SLE nephritis are planned or any new therapeutic modality is evaluated.     

Reversible acute renal failure associated with clomipramine-induced interstitial nephritis

We describe a 41-year old man with obsessive-compulsive neurosis who developed acute renal failure (ARF) due to acute interstitial nephritis (AIN) during 6 weeks of treatment with clomipramine hydrochloride (CPH). He had a slight fever, mild arthralgia, appetite loss, and diarrhea after taking CPH. On admission, he showed serum creatinine (sCr) of 7.31 mg/dl, and creatinine clearance (Ccr) of 2.5 ml/min. He subsequently became anuric and required hemodialysis. Renal biopsy revealed AIN with diffuse mononuclear cell infiltration. After the withdrawal of CPH and treatment with prednisolone (PSL) 0.5 mg/kg per day, his urinary output improved, along with improvement of his renal function; therefore hemodialysis was finally discontinued. To our knowledge, this is the first case report of AIN induced by clomipramine.     

Successful relatively low-dose corticosteroid therapy for diclofenac-induced acute interstitial nephritis with severe renal failure

We report a case of nephrotic syndrome and acute renal failure that developed in a 73-year-old woman after six months of treatment with the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Renal biopsy revealed interstitial nephritis and minimal change nephropathy. Despite discontinuation of treatment with diclofenac, she subsequently became anuric and required hemodialysis for progressive azotemia. Since her anuria was persistent, treatment with prednisone at a dose of 30 mg/day was started. With progressive increase in urine output after the initiation of corticosteroid treatment, a constant decrease in serum creatinine was observed along with improvement of creatinine clearance. In addition, the increased urinary excretion of beta2-microglobulin (beta2MG) and N-acetyl-beta-D-glucosaminidase (NAG) on admission was also improved during the treatment. Our findings suggest that corticosteroid treatment should be reserved for patients with the protracted deterioration of renal function even after discontinuation of offending trigger agents.     

The natural history of renal function in untreated idiopathic membranous glomerulonephritis in adults

Sixty-four patients (47 male, 17 females) aged between 20 and 70 years with idiopathic membranous glomerulonephritis, never having received steroid or immunosuppressive drugs prior to and subsequent to biopsy, have been followed to terminal renal failure or for a minimum of two up to fifteen years. Presentation was with asymptomatic proteinuria in 12 and nephrotic syndrome in 52. The serum creatinine at time of biopsy was less than or equal to 99 mumoles/l in 25, 100-119 mumoles/l in 18 and greater than or equal to 120 mumoles/l in 21. During the follow up there was no deterioration in renal function in 30 patients (48%). In 27 patients (43.5%) there was a steady deterioration in renal function, on the average 30 months (range 5-60) for the serum creatinine to double and 32 months (range 5-49) for the serum creatinine to reach 400 mumoles/l. In five patients there was a slow deterioration. A plot of the reciprocal of the sequential serum creatinine values with time indicates that the rate of deterioration is essentially constant in any patient but that there is a wide variation between patients. The reciprocal of the serum creatinine is a useful means of following the evolution of the disease. In two patients there was a change in the rate of deterioration and a cause could be identified (one with renal vein thrombosis, one with interstitial nephritis). Poor prognostic indicators were: nephrotic syndrome at presentation, impaired function at time of diagnosis, male patients and older age.