Women and CKD-mineral and bone disorder.

Development of CKD-mineral and bone disorder (MBD) increases morbidity and mortality in men and women with CKD. The corresponding link among bone disease, fracture, and extraskeletal calcifications has been the subject of much focus. In the general population, the incidence of cardiovascular disease is higher in men than women, and this gender differences in degree of calcification and morbidity is maintained in kidney disease. Gender differences in phosphorus and fibroblast growth factor-23 (FGF-23) have been described. Increases in both have been linked with increasing likelihood of death in the CKD population as a whole; however, this link is not as well described when looking at women alone. The clinical significance of these differences, and the potential associated outcomes, are poorly understood. Traditional understanding of bone disease in women without kidney disease may not be fully applicable in women with CKD. Use of bone densitometry is limited in this population, and the traditional preventative interventions may not be fully transferrable to women with CKD.

A case of simultaneous, biopsy-proven, classic, ANCA-positive Wegener's granulomatosis and anti-GBM disease, but without detectable circulating anti-GBM antibodies.

Wegener's granulomatosis (WG) is a systemic, necrotizing, granulomatous vasculitis of unknown etiology. Approximately 75% of cases present as classic WG with both pulmonary and renal involvement, while the remaining 25% of patients present with a limited form with either predominantly upper or lower respiratory tract symptoms. Ninety percent of WG patients have circulating anti-neutrophil cytoplasmic antibodies (ANCA), and approximately 10% have both circulating ANCA antibodies and concomitant anti-glomerular basement membrane (anti-GBM) disease on renal biopsy. Virtually all of these patients also have circulating anti-GBM antibodies. While it has been reported that some patients with ANCA vasculitis have circulating anti-GBM antibodies, and patients with anti-GBM disease may have positive ANCA, review of the literature does not demonstrate other cases of biopsy-proven, simultaneous, ANCA-associated vasculitis and anti-GBM disease. We report a case of simultaneous, biopsy-proven, classic, ANCA-positive WG and anti-GBM disease, but without detectible circulating anti-GBM antibodies. We present findings characteristic of both WG and linear IgG deposition along the GBM suggesting concurrent anti-GBM disease, in the absence of detectable circulating anti-GBM antibodies. Possible theories to explain the absence of these antibodies are discussed.

Impact of ergocalciferol treatment of vitamin D deficiency on serum parathyroid hormone concentrations in chronic kidney disease.

BACKGROUND: Vitamin D deficiency is highly prevalent and associated with secondary hyperparathyroidism in patients with chronic kidney disease (CKD). The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend treatment of vitamin D deficiency starting with CKD stage 3, though no data are available showing an impact on serum parathyroid hormone (PTH) concentrations. The goal of this analysis, therefore, was to determine the effect of ergocalciferol treatment on plasma PTH concentrations in vitamin D-deficient patients with stage 3 and stage 4 CKD. METHODS: A prospective, nonrandomized observational analysis was conducted in an academic community hospital CKD clinic. Fifty-two patients with stage 3 or stage 4 CKD with vitamin D deficiency and elevated PTH concentrations received ergocalciferol dosed per a modified K/DOQI guidelines protocol and adjusted every 3 months. Serum PTH, 25-vitamin D, 1,25-vitamin D, calcium, phosphorus, and albumin levels were drawn at initiation of therapy and repeated every 3 months. RESULTS: The mean 25-vitamin D levels normalized in patients with stage 3 and 4 CKD, with values of 31.6 +/- 2.2 ng/ml (78.8 +/- 5.49 nmol/l) and 35.4 +/- 1.9 ng/ml (88.4 +/- 4.74 nmol/l), respectively (p < 0.0001). A median decrease in PTH concentrations of 13.1 and 2.0% was noted in patients with stage 3 and stage 4 CKD, respectively (p = 0.041, p = nonsignificant). CONCLUSIONS: Ergocalciferol therapy is a reasonable initial therapy for vitamin D deficiency associated with elevated PTH levels in stage 3 CKD. It does not appear to have equivalent benefits in stage 4 CKD.

Familial Mediterranean fever, inflammation and nephrotic syndrome: fibrillary glomerulopathy and the M680I missense mutation.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by inflammatory serositis (fever, peritonitis, synovitis and pleuritis). The gene locus responsible for FMF was identified in 1992 and localized to the short arm of chromosome 16. In 1997, a specific FMF gene locus, MEFV, was discovered to encode for a protein, pyrin that mediates inflammation. To date, more than forty missense mutations are known to exist. The diversity of mutations identified has provided insight into the variability of clinical presentation and disease progression. CASE REPORT: We report an individual heterozygous for the M680I gene mutation with a clinical diagnosis of FMF using the Tel-Hashomer criteria. Subsequently, the patient developed nephrotic syndrome with biopsy-confirmed fibrillary glomerulonephritis (FGN). Further diagnostic studies were unremarkable with clinical workup negative for amyloidosis or other secondary causes of nephrotic syndrome. DISCUSSION: Individuals with FMF are at greater risk for developing nephrotic syndrome. The most serious etiology is amyloidosis (AA variant) with renal involvement, ultimately progressing to end-stage renal disease. Other known renal diseases in the FMF population include IgA nephropathy, IgM nephropathy, Henoch-Schönlein purpura as well as polyarteritis nodosa. CONCLUSION: To our knowledge, this is the first association between FMF and the M680I mutation later complicated by nephrotic syndrome and fibrillary glomerulonephritis.

Renal osteodystrophy in chronic renal failure.

Bone disease develops relatively early in the development of chronic renal failure. Much of what is known about the evaluation and management of renal osteodystrophy in chronic renal failure is based on knowledge obtained in the dialysis population. The classic bone lesion found in the dialysis population is osteitis fibrosa, the high turnover lesion of secondary hyperparathyroidism. Clearly, hypocalcemia, hyperphosphatemia, and calcitriol deficiency play major roles in the development and maintenance of the high turnover disease. Interestingly, in both the dialysis and nondialysis patients, the incidence of adynamic bone disease, a low turnover lesion, is increasing. It is postulated that the aggressive use of calcium-containing phosphate binders and the use of calcitriol and other vitamin D analogs to treat secondary hyperparathyroidism may contribute to this shift in bone lesions. Treatment in the nondialysis kidney disease patient remains aggressive correction of hypocalcemia and hyperphosphatemia. The use of calcitriol and other agents to maintain serum calcium and to suppress elevated parathyroid hormone remains well supported. However, the increase in extraskeletal calcifications and incidence of adynamic bone disease in these patients raises concern about current management techniques.