Sarcoidosis presenting with hearing loss and granulomatous interstitial nephritis in an adolescent

Granulomatous interstitial nephritis is an uncommon finding in a kidney biopsy. The differential diagnosis is broad and includes infections, drug exposure, and sarcoidosis. Sarcoidosis, a systemic disorder of unknown etiology characterized by the presence of noncaseating granulomata in affected organs, is rare in children. We discuss an adolescent boy with the unusual presentation of granulomatous interstitial nephritis and acute deafness. Sarcoidosis should be considered as part of the differential diagnosis for children and adolescents with hearing loss and kidney disease.     

A case of sarcoid granulomatous interstitial nephritis improved by steroid therapy]

We report a case of sarcoid granulomatous tubulointerstitial nephritis diagnosed by renal biopsy. A 60-year-old man presented with productive cough, and exertional dyspnea of 3 months duration. A chest X-ray film revealed diffuse reticulonodular infiltrates in both lung fields. A transbronchial lung biopsy specimen showed inflammation of the alveolar septum associated with non-caseating granulomas. The patient also had tubular proteinuria and glucosuria. Ga-scintigraphy demonstrated an abnormal accumulation of gallium in both lungs and kidneys. Renal function tests revealed tubular dysfunction. Tubulointerstitial nephropathy was suspected. A renal biopsy specimen exhibited tubulointerstitial nephritis associated with numerous non-caseating granulomas, similar to the findings of the lung biopsy specimen. No glomerular abnormalities were evident. Later, a scalene node biopsy confirmed the diagnosis of sarcoidosis. Prednisolone therapy yielded a favorable outcome for both the renal and pulmonary involvement. During the corticosteroid therapy, measurement of the urinary beta-2-microglobulin concentration proved a valuable monitoring tool for assessing the recovery of the tubular impairment.     

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.     

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.     

Renal sarcoidosis presenting as acute kidney injury with granulomatous interstitial nephritis and vasculitis

Among the various renal manifestations of sarcoidosis, granulomatous inflammation confined to the tubulointerstitial compartment is the most commonly reported finding. We present the case of a 66-year-old man with acute kidney injury, hypercalcemia, mild restrictive pulmonary disease, and neurologic signs of parietal lobe dysfunction. Kidney biopsy showed diffuse interstitial inflammation with noncaseating granulomas that exhibited the unusual feature of infiltrating the walls of small arteries with destruction of the elastic lamina, consistent with granulomatous vasculitis. The findings of granulomatous interstitial nephritis on kidney biopsy, hypercalcemia, and possible cerebral and pulmonary involvement in the absence of other infectious, drug-induced, or autoimmune causes of granulomatous disease established the diagnosis of sarcoidosis. Pulse methylprednisolone followed by maintenance prednisone therapy led to improvement in kidney function, hypercalcemia, and neurologic symptoms. Vasculocentric granulomatous interstitial nephritis with granulomatous vasculitis is a rare and under-recognized manifestation of renal sarcoidosis.     

Sodium-valproate-induced interstitial nephritis

A 5-year-old Chinese girl had had absence seizures and received sodium valproate (VPA) treatment which provided good control. Six months later, she developed interstitial nephritis with proteinuria and microhematuria. Renal biopsy revealed interstitial nephritis with granular deposition of immunoglobulin G (IgG) and C3 in the renal tubular basement membrane (TBM). Ultrastructurally, dilated smooth endoreticular cisternae with mitochondrial degeneration in the tubular cells and scattered electron-dense deposits within the TBM were also noted. Serum circulating immune complexes were detectable, ACH50 and properdin factor B increased. Mononuclear cells (MNC) from the patient after in vitro incubation with VPA (100 micrograms/ml) induced interleukin-2 (IL-2) production and lymphoproliferative response. However, there was no response in controls. The serum VPA level ranged from 84 to 92 micrograms/ml. After VPA was stopped, the microhematuria and proteinuria disappeared. These observations indicate that VPA-induced interstitial nephritis represents a sequence of interrelationships among multiple immunologic factors.     

Mesalazine-associated interstitial nephritis

BACKGROUND.: When used for oral treatment of inflammatory bowel disease,Asacol (a coated form of mesalazine = 5-aminosalicylic acid)can cause interstitial nephritis. The spectrum of severity,frequency of occurrence and the best renal function test todetect this complication are not known. The value of immunosuppressionin addition to drug withdrawal is similarly undetermined. METHODS.: Four cases of interstitial nephritis which occurred in associationwith oral Asacol treatment are presented and a further 12 caseswho received similar treatment are reviewed. Clinical trialspublished previously were scrutinized to assess the frequencyof impaired renal function. RESULTS.: The available evidence suggests that renal impairment of anyseverity may occur in up to 1 in 100 patients, but that clinicallysignificant interstitial nephritis occurs in less than 1 in500 patients. This is most reliably detected by an elevatedserum creatinine concentration. If the diagnosis of nephrotoxicityis delayed until 18 months after commencement of medication,restoration of renal function, which is seen on withdrawal ofmedication alone up to 10 months, does not occur and there isno evidence to date to indicate that addition of immunosuppressionconfers any significant advantage at this later stage. CONCLUSIONS.: It is suggested that serum creatinine concentration should bemeasured each month for the first 3 months of treatment, 3-monthlyfor the remainder of the first year and annually thereafter.The use of concurrent immunosuppressive therapy may necessitateextension to the period of intensive monitoring. Any elevationof serum creatinine which cannot be related to a relapse ofinflammatory bowel disease should prompt immediate withdrawalof Asacol and related medications and substitution of alternativetherapy. Neither the lack of urinary abnormalities on routinetesting nor the absence of clinical or laboratory features ofdrug allergy can be relied upon to rule out interstitial nephritisduring oral therapy with these drugs.     

Chronic renal failure due to granulomatous interstitial nephritis in sarcoidosis: Response to corticosteroid therapy

Chronic renal failure due to granulomatous interstitial nephritis in sarcoidosis is a rare phenomenon, and its response to corticosteroid therapy is not well known. We report a patient with sarcoidosis who presented with chronic renal failure and hypercalcemia, but who did not exhibit nephrocalcinosis. Renal histology findings showed the presence of noncaseating granuloma and heavy interstitial nephritis. Although hypercalcemia was remarkably improved by corticosteroid therapy, chronic renal failure, due to interstitial fibrosis and scarring, remained unchanged. This case reinforces evidence supporting the effectiveness of corticosteroid therapy in granulomatous interstitial nephritis of sarcoidosis, and suggests the need for early initiation of the therapy to avoid permanent renal dysfunction.     

Renal failure with granulomatous interstitial nephritis and diffuse leukemic renal infiltration in chronic lymphocytic leukemia

Renal dysfunction is uncommon in patients with leukemic infiltration of the kidney due to Chronic Lymphocytic Leukanemia (CLL). Granulomatous interstitial nephritis (GIN) is also rare, but a characteristic hallmark of certain diseases such as sarcoidosis and tuberculosis. GIN has been associated with medications, infections, inflammation, Wegener's granulomatosis, and jejuno-ileal bypass. GIN combined with leukemic infiltration by CLL is very uncommon. We present a 72-year-old male with Binet stage A CLL who developed progressive renal failure over a period of four years requiring maintenance dialysis. During the course of his illness, he underwent renal biopsies at different time intervals, revealing varying degrees of involvement by GIN together with leukemic infiltration.     

Carbamazepine-induced acute granulomatous interstitial nephritis

A 79-year-old man, newly started on carbamazepine, presented with rash, eosinophilia and liver dysfunction progressing to acute renal failure despite discontinuation of the anti-epileptic agent. Percutaneous renal biopsy revealed acute granulomatous interstitial nephritis, which responded successfully to high-dose oral steroid therapy.     

Drug hypersensitivity causing granulomatous interstitial nephritis

In association with treatment for pharyngitis, a 47-year-old white man developed a systemic illness with fever, myalgia, episcleritis, hemoptysis, pleurisy, eosinophilia, and renal impairment. Renal biopsy revealed granulomatous interstitial nephritis, which resolved due to no specific treatment other than withdrawing all medication. Both the severe systemic manifestations and spontaneous recovery are unusual in association with drug-induced granulomatous nephritis. The drugs that may have caused the reaction included dihydrocodeine, phenylpropanolamine, erythromycin, and amoxycillin. Although the latter three drugs have been previously implicated in the development of interstitial nephritis, there have been no previous reports of granulomatous interstitial nephritis with any of these drugs.     

Acute granulomatous interstitial nephritis due to co-trimoxazole

A 51-year-old man with diabetes mellitus and mild hypertension developed acute interstitial nephritis 4 days after starting a course of co-trimoxazole for bronchopneumonia. Following initial symptoms of overt hypersensitivity, he developed azotemia and renal tubular dysfunction with malaise and anorexia requiring hospitalization. Renal pathology demonstrated an acute granulomatous interstitial nephritis superimposed on chronic diabetic renal disease.     

Drug-induced granulomatous interstitial nephritis in a pediatric patient

Acute interstitial nephritis (AIN) is a known cause of acute renal failure in children. In most instances, drug therapy is the offending agent. Although granuloma formation has been observed in drug-induced interstitial nephritis, it is not a commonly associated manifestation. This is a case of a 15-year-old white female with Tetralogy of Fallot and pulmonary atresia who developed acute renal failure secondary to drug-induced interstitial nephritis and renal granulomas. In addition to interstitial edema with eosinophils and lymphocytes, her renal biopsy showed interstitial granulomas, immune complexes within tubular basement membranes, and the unusual feature of multinucleated giant cells engulfing tubules. Her acute renal failure resolved after the withdrawal of antibiotics and the initiation of intravenous steroid therapy.     

Acute granulomatous interstitial nephritis secondary to bisphosphonate alendronate sodium

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and is characterized by a progressive accumulation of functionally incompetent monoclonal lymphocytes. Renal involvement has been described in CLL but is uncommon. Granulomatous interstitial nephritis is a rare but characteristic hallmark of certain diseases such as sarcoidosis and tuberculosis. These epithelial reactions have also been reported with medications, infections, inflammation, Wegener's granulomatosis, and jejunoileal bypass. We present a 74-year-old woman with a stage 0 chronic lymphocytic leukemia who developed acute renal failure following the initiation of alendronate. The renal biopsy revealed an acute granulomatous interstitial nephritis. Infectious and inflammatory etiologies were ruled out. Hemodialysis was required despite discontinuation of all medications. Partial recovery of renal function occurred after 6 weeks of prednisone therapy and cyclophosphamide. This report describes a unique case of acute granulomatous interstitial nephritis and leukemic cell kidney infiltration by CLL.     

Membranous nephropathy and granulomatous interstitial nephritis due to tuberculosis

Tuberculous involvement of the genitourinary tract is well reported in the literature. However, reports of glomerular lesions of the kidney due to tuberculosis are rare. Tuberculosis has been identified as the most common infectious cause of granulomatous interstitial nephritis (GIN). We report a 23-year-old female patient with a membranous nephropathy and GIN due to tuberculosis. She presented with renal failure and nephrotic-range proteinuria, both of which resolved with the treatment of tuberculosis. There is only one report, from Japan, of a patient with membranous nephropathy and tuberculous granulomatous nephritis. Our patient is the second with tuberculous GIN and membranous nephropathy. In our patient, the close temporal relationship between the infection and glomerulonephritis, an ulcerated tuberculin skin test, the response to the treatment and the absence of any other systemic disease that might cause the glomerulonephritis suggested an association between tuberculosis and membranous nephropathy. However, a causal association can only be speculation, because membranous nephropathy could remit spontaneously. It is also possible that it might relapse at a later date when the tuberculosis is inactive. Therefore, the association might be either coincidental or causal, and could become clearer as similar patients are reported.