Renal confined sarcoidosis: Natural history and diagnostic challenge
The present case report is about a 69-year-old male patient who was referred to nephrology for persistent and worsening hypertension for 2 years despite taking multiple anti-hypertensive medications. No other complaints. Past medical history included obstructive sleep apnea, diabetes mellitus type 2, atrial fibrillation, hypothyroidism, gastro esophageal reflux disease, renal cysts, fatty liver, gout, dyslipidemia and benign prostatic hyperplasia. Social history and family history were unremarkable.\nPatient had negative 24 urinary catecholamines, arterial Doppler studies of the renal arteries and renal computed tomographic angiography. Initial ancillary laboratory findings were unremarkable including renin, aldosterone, parathyroid hormone (PTH) and calcium levels. He had borderline normal renal function (serum creatinine = 1.2, glomerular filtration rate [GFR] >60). Urinalysis was normal. Blood pressure improved to normal on atenolol, nifedipine, lisinopril. Patient also demonstrated low vitamin D 25-hydroxy levels and was consequently started on replacement with ergocalciferol.\nWithin 6 months of initial nephrology work-up, the patient continued to demonstrate stable blood pressure, renal function and blood counts.\nUnexpectedly, 8 months later, the patient's GFR dropped to 58 and he had slight anemia with hemoglobin level of 12.9. Blood pressure remained stable. His calcium, PTH and vitamin D - 25 levels were all within the normal limits. Around 10 months post referral, serum protein electrophoresis demonstrated an IgG kappa monoclonal spike and GFR decreased to 55 (chronic kidney disease stage 3). His calcium and PTH were normal. Urinalysis was negative except for monoclonal IgG on immunoelectrophoresis, but no light chains detected. At this time, patient was referred to hematology-oncology specialist and a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) was established through bone marrow biopsy. Final pathologic diagnosis was: A, B, C. Bone marrow, aspirate/imprint smears, clot and biopsy sections, Hypercellular marrow for age (80% cellularity) with increased myelopoiesis and mild dysmegakaryopoiesis. Absent iron stores, marrow, with decreased sideroblastic iron, compatible with iron deficiency anemia pattern. Less than 10% plasma cells with kappa excess (by CD138 and kappa/lambda immunostaining), most compatible with a MGUS.\nAt approximately 16 months later, the patient stated noticing elevated blood pressure reading and started to develop symptoms of malaise and fatigue. Within 2 months (18-20 months post-nephrology referral), the patient's renal function declined abruptly (GFR 32) and was also demonstrating bone mineral disease with worsening hypercalcemia (calcium 10.6 mg/dL) and low PTH (<1 pg/mL) [Graphs and ].\nGiven the history of monoclonal gammopathy, the concern and working diagnosis included the possibility of a plasma cell dyscrasia. However, repeat serum protein electrophoreses was not impressive and anemia was only mild (12.6). The oncologist suggested that worsening calcium levels and renal failure could represent milk alkali syndrome, given dietary history where the patient was consuming three glasses of milk per day. Within the next 3 months (21-23 months post nephrology referral), the calcium levels slightly dropped after the cessation of milk intake, but rebounded again with no identifiable cause (calcium 10.7). More importantly, the renal function showed significant aberration and decline within these months (GFR was 8); necessitating dialysis for end-stage renal disease (ESRD) and a drastic revision in diagnostic approach.\nRepeated renal ultrasound showed cortical atrophy and no hydronephrosis. Chest radiographic imaging was negative and skeletal survey was showed no lytic or other bone related lesions. Renal biopsy was ordered due to unexplained and unexpected worsening of renal function.\nH and E, periodic acid-Schiff, Lillie's allochrome and Jones' silver stained section of the renal cortex and medulla. Evaluation demonstrated diffuse tubular atrophy involving 90% of tubules examined. The luminae contained cellular debris or protein casts with cellular response [].\nMononuclear cell infiltrates with non-necrotizing granulomatous inflammation and eosinophils were noted-granulomatous interstitial inflammation with eosinophils [].\nDirect immunofluorescence with fluorescein isothiocyanate conjugated antisera (IgG, IgA, IgM, C3, C1q, albumin, fibrinogen and kappa and lambda light chains revealed no glomerular or tubulointerstitial staining. This aforementioned finding excludes immune complex glomerulonephritis [].\nAnalysis of one glomerulus selected for examination demonstrated no electron dense deposits, no amyloid type fibrils, no tubuloreticular inclusions and normal thickness of glomerular basement membrane.\nNegative stain to detect for mycobacteria or other acid fast organisms.\nThe significant finding obtained from renal biopsy revealed granulomatous interstitial inflammation with eosinophils consistent with renal sarcoidosis. His purified protein derivative skin test was negative.\nHis angiotensin converting enzyme (ACE) level was high (73 units/L) and PTH level was still low (4 pg/mL) 24 months after the initial referral. Vitamin D1/25 dihydroxy level was checked later and was elevated (148 pg/mL).\nIn light of ESRD and a conclusive diagnosis of renal-confined sarcoidosis, the patient was begun on prednisone (60 mg daily) and enrolled in a hemodialysis program. Within 1 month, the patient's hypercalcemia resolved and remained within normal values up to 3 years for a majority of the time-course. ACE, PTH and vitamin D1/25 dihydroxy improved as well. Despite the improvement of his calcium, the patient's renal function continued to be refractory to steroid treatment and remained on dialysis for persistent ESRD.