[Skip to Navigation]
Sign In
Special Feature
December 1999

Pathological Case of the Month

Arch Pediatr Adolesc Med. 1999;153(12):1307-1308. doi:

Diagnosis and Discussion: Diabetic Nephropathy in Cystic Fibrosis

Figure 1. Microscopic section of the renal biopsy specimen showing mesangial hypercellularity and matrix increase. Glomerular arterioles exhibit hyaline change (hematoxylin-eosin, original magnification ×200.)

Figure 2. Microscopic section showing increased mesangial matrix (Masson trichrome, original magnification ×200).

Figure 3. Microscopic section showing mild atherosclerosis (hematoxylin-eosin, original magnification ×220).

Figure 4. Electron photomicrograph demonstrating mildly thickened glomerular basement membranes and increased mesangial matrix (uranyl acetate–lead citrate, original magnification ×15,000).

Figure 5. Electron photomicrograph showing rare dense deposits in glomerular capillary loops (uranyl acetate–lead citrate, original magnification ×35,000).

The clinical history of DM implied that the glomerular, tubulointerstitial, and vascular scarring in this young patient was owing in part to early progression of diabetic nephropathy. A superimposed, mediated immune complex glomerulonephritis characterized by mesangial proliferation and rare immune deposits was present in the glomerular basement membranes (GBMs) and mesangia. The mesangial hypercellularity and distribution of sparse immune deposits, some of which were rarefied, suggested resolving postinfectious glomerulonephritis. This interpretation derives support from Abramowsky and Swinehart,1 who attributed similar mesangiopathic lesions to a postinfectious process in their study of nephropathy in young patients with CF.

Diabetes mellitus nephropathy is characterized pathologically by histologic changes that occur in the GBMs, mesangial matrix, and vasculature. The GBM is thickened by a homogeneous hyaline structure that is periodic acid–Schiff positive. Mild proliferation of mesangial cells with notable matrix increase when combined with thickened GBM leads to diffuse glomerulosclerosis. The pathogenesis of the disease is hypothesized to be due to 4 factors: (1) metabolic defect of increased glucose or decreased insulin with direct effects; (2) increased type IV collagen and fibronectin in the GBM with decreased proteoglycan; (3) new enzymatic glycosylation of proteins, ie, the GBM collagen; and (4) increased glomerular filtration rate and glomerular hypertrophy.2

The increased life expectancy of patients with CF observed over the last 25 years has been associated with an increased prevalence of DM in the population with CF.3 Patients with CF with long-standing DM are at increased risk for developing microangiopathic effects on the eyes, kidneys, and nervous system much like patients with DM without CF.

Reports from 6 studies4-9 of patients with CF found that 4.9% to 14.7% of patients with CF were clinically diagnosed as having DM. The CF genotype also seems to play a major role in the development of DM in patients with CF. Rosenecker et al4 found that 75% and 19% of 39 patients with CF and DM, respectively, had homozygous and heterozygous ΔF508 gene deletions. Age of onset tends to be in the second decade of life, but has been reported as early as age 2 years.10 The cause of diabetes in patients with CF has been attributed to decreased beta-islet cell number and reduced insulin levels and C-peptide activity.11 Insulin resistance has been noted to influence glucose tolerance in CF.12 Pancreatic fibrosis along with these other pancreatic changes are believed to play a major role in the incidence of DM in patients with CF.

Diabetic microangiopathy, as in our patient, is becoming more important as longevity increases for patients with CF. Sullivan and Denning11 studied 19 patients with CF and DM from 1978 through 1987 and found that 4 (21%) had microangiopathic complications secondary to DM. This development of multisystem microvascular disease in 3 patients after having DM for 10 years is similar to the pattern seen in patients with DM without CF.11 Our patient's presentation was atypical and accelerated compared with the usual documented progression of complications from DM. As with this patient, the clinician needs to be increasingly alert for presentations of microangiopathic changes of DM in patients with CF who have DM.

Accepted for publication April 30, 1999.

Reprints: Mark Weatherly, MD, Nemours Children's Foundation, 83 W Columbia St, Orlando, FL 32806.

Abramowsky  RSwinehart  GL The nephropathy of cystic fibrosis: a model of chronic nephrotoxicity.  Hum Pathol. 1982;13934- 939Google ScholarCrossref
Cotran  RSKumar  VRobbins  SL Robbin's Pathologic Basis of Disease.  Philadelphia, Pa WB Saunders Co1994;961- 963
Rodman  HMDoershuk  CFRoland  JM The interaction of two diseases: diabetes mellitus and cystic fibrosis.  Medicine (Baltimore). 1986;65389- 397Google ScholarCrossref
Rosenecker  JEichler  IKuhn  L  et al.  Genetic determination of diabetes mellitus in patients with cystic fibrosis.  J Pediatr. 1995;127441- 443Google ScholarCrossref
Reisman  JCorey  MCanny  G  et al.  Diabetes mellitus in patients with cystic fibrosis: effect on survival.  Pediatrics. 1990;86374- 377Google Scholar
Finkelstein  SMWielinski  CLElliot  GR  et al.  Diabetes mellitus associated with cystic fibrosis.  J Pediatr. 1988;112373- 377Google ScholarCrossref
Kreuger  LJLerner  AKatz  SM  et al.  Cystic fibrosis and diabetes mellitus: interactive or idiopathic?  J Pediatr Gastroenterol Nutr. 1991;13209- 219Google ScholarCrossref
Hayes  FJO'Brien  AO'Brien  C  et al.  Diabetes mellitus in an adult cystic fibrosis population.  Ir Med J. 1994;8759- 60Google Scholar
Lanng  SThorsteinsson  BLund-Anderson  C  et al.  Diabetes mellitus in Danish cystic fibrosis patients: prevalence and late diabetic complications.  Acta Paediatr. 1994;8372- 77Google ScholarCrossref
Pfeifer  T Diabetes in cystic fibrosis.  Clin Pediatr. November1992;682- 687Google Scholar
Sullivan  MMDenning  CR Diabetic microangiopathy in patients with cystic fibrosis.  Pediatrics. 1989;84642- 647Google Scholar
Culler  FLMcKean  LPBuchanan  CN  et al.  Glipizide treatment of patients with cystic fibrosis and impaired glucose tolerance.  J Pediatr Gastroenterol Nutr. 1994;18375- 378Google ScholarCrossref