Nodular Glomerulosclerosis in Cystic Fibrosis Mimics Diabetic Nephropathy

Abstract

Background/Aims: Despite the cystic fibrosis gene product, the cystic fibrosis transmembrane conductance regulator, being widely expressed throughout the kidney, there is no clearly defined renal phenotype in patients with cystic fibrosis. As patients with cystic fibrosis survive longer progressive pancreatic destruction may lead to abnormal glucose tolerance and diabetes mellitus, which in the kidney may be associated with the characteristic changes of nodular glomerulosclerosis. Methods: The adult cystic fibrosis service at the Alfred hospital consists of a cohort of 200 patients. We describe 3 cystic fibrosis patients with impaired renal function who had renal biopsies performed as part of their diagnostic work-up. All patients had fasting plasma glucose levels, oral glucose tolerance tests and measurements of HbA_1c performed to assess for the presence of cystic fibrosis-related diabetes mellitus. Results: The renal biopsies of all 3 patients showed histological changes characteristic of diabetic nephropathy. In all cases described characteristic Kimmelstiel-Wilson nodules were present. However, in all 3 patients the presence of impaired glucose tolerance and diabetes mellitus was excluded using standard biochemical diagnostic criteria. Conclusion: We describe 3 adult CF patients, who on renal biopsy had histological evidence of nodular glomerulosclerosis in the absence of abnormal glucose metabolism. We speculate that the pro-inflammatory cytokine profile, typical of cystic fibrosis, predisposes to the lesions described.

Renal vascular Doppler ultrasonographic indices and carotid artery intima-media thickness in diabetic nephropathy

“…However, we found no statistically significant relationship between the CCIMT and the severity of diabetic nephropathy, albuminuria, conventional and Doppler US findings. The observation is in contrast with a previous published study [27] and can be attributed to the difference in the severity of diabetic nephropathy and the presence of renal failure in the study group…”

Nodular Glomerulosclerosis in the Nondiabetic Smoker

“…Differential diagnosis includes the entities listed in Table 1. [1][2][3] In our case, the absence of immune deposits by immunofluorescence excluded chronic membranoproliferative glomerulosclerosis-and dysproteinemia-related glomerulopathies. By electron microscopy, no organized deposits were seen.…”

“…Medications included metoprolol, furosemide, amlodipine besylate, and home oxygen (4 L/min). Pertinent laboratory results included white blood count 17,700/mm 3 (normal range 4000 to 11,000/mm 3 ), glucose 62 mg/dl (normal range 70 to 110 mg/dl), serum albumin 3.2 g/dl (normal range 3.5 to 4.9 g/dl), and serum cholesterol 113 mg/dl (normal range 130 to 200 mg/dl). The 24-h urine protein was 2.1 g. All serologies were negative, and no M spike was detected on serum protein electrophoresis.…”

Renal Involvement in Cystic Fibrosis

“…These data, as well as the fact that patients with diabetes may present with nondiabetic nephropathy (patients 7, 8, 12, and 13), plead once again for large indications for renal biopsies in patients with CF, including those with diabetes. Characteristic KW nodular glomerulosclerosis has been rarely reported in patients with CF in the absence of abnormal glucose metabolism and may be related to the inflammatory cytokine profile present in patients with CF (17). This peculiar pathologic feature also was recently associated with hypertension, smoking, and metabolic syndrome (18).…”