Cystatin C is a sensitive marker for detecting a reduced glomerular filtration rate when assessing chronic kidney disease in patients with rheumatoid arthritis and secondary amyloidosis.

OBJECTIVE: Chronic kidney disease is a predictor of end-stage renal disease, and evaluating the glomerular filtration rate (GFR) is necessary to make a definite diagnosis. We assessed the utility of serum cystatin C (cysC) for identifying a reduced GFR in patients who have rheumatoid arthritis (RA) with secondary amyloidosis. METHODS: Fifty patients with RA and secondary amyloidosis (mean age 60.9+/-11.2 years; 45 women) were evaluated. The revised 24-h creatinine clearance (r24-hC(Cr)), which was determined by multiplying the original value by 0.719, was used as a reference for the GFR. The screening potential of the serum cysC and some estimates of the GFR calculated from the serum cysC (cysC-eGFR: eGFR(Hoek) and eGFR(Rule)) for detecting a reduced GFR (r24-hC(Cr)<60 mL/min/1.73 m(2)) were analysed. RESULTS: Both cysC-eGFRs were strongly correlated with the r24-hC(Cr) (eGFR(Hoek), r=0.846, p<0.001; eGFR(Rule), r=0.820, p<0.001). The difference between the average eGFR(Rule) (37.1+/-31.2 mL/min/1.73m(2)) and average r24-hC(Cr) (35.3+/-30.9 mL/min/1.73 m(2)) was small, whereas eGFR(Hoek) and sCr-eGFR were higher than eGFR(Rule) and r24-hC(Cr). In receiver operating characteristic (ROC) curve analyses of a reduced GFR, serum cysC gave a greater area under the curve (AUC=0.958) than the sCr-eGFR (0.939-0.942). The specificity and positive predictive value (PPV) reached 100% when serum cysC >1.365 mg/L was used. CONCLUSIONS: Serum cysC can identify a reduced GFR more accurately than sCr-eGFRs. Serum cysC >1.09 mg/L (i.e. eGFR(Rule)<60 mL/min/1.73 m(2)) could be a marker of a reduced GFR, and serum cysC >1.365 mg/L would strongly suggest a reduced GFR in patients who have RA with secondary amyloidosis.

Etiology and prognostic significance of severe uremic pruritus in chronic hemodialysis patients.

Although uremia is well known as the most common cause of pruritus, the mechanisms of pruritus in chronic hemodialysis patients remain unclear. The purpose was to characterize uremic pruritus in more detail and to investigate whether severe pruritus is a marker for poor prognosis. A total of 1773 adult hemodialysis patients were studied. A questionnaire was given to each patient to assess the intensity and frequency, as well as pruritus-related sleep disturbance. We analyzed the relationship between clinical and laboratory data and the severity of pruritus in hemodialysis patients and followed them for 24 months prospectively. In total, 453 patients had severe pruritus with a visual analogue scale (VAS) score more than or equal to 7.0. Among them, more than 70% complained of sleep disturbance, whereas the majority of patients with a VAS score of less than 7.0 had no sleep disturbance. Male gender, high levels of blood urea nitrogen, beta2-microglobulin (beta2MG), hypercalcemia, and hyperphosphatemia were identified as independent risk factors for the development of severe pruritus, whereas a low level of calcium and intact-parathyroid hormone were associated with reduced risk. During the follow-up, 171 (9.64%) patients died. The prognosis of patients with severe pruritus was significantly worse than the others. Moreover, severe pruritus was independently associated with death even after adjusting for other clinical factors including diabetes mellitus, age, beta2MG, and albumin. Severe uremic pruritus caused by multiple factors, not only affects the quality of life but may also be associated with poor outcome in chronic hemodialysis patients.

Transforming growth factor-beta1 gene polymorphism modifies the histological and clinical manifestations in Japanese patients with IgA nephropathy.

Transforming growth factor (TGF)-beta1, a multifunctional cytokine, which regulates proliferation and differentiation of a variety of cell types, has the central role in the development and progression of renal injury in both animal models and human. Although it has been suggested that genetic variations in the TGF-beta1 gene are associated with the activity of the gene product, their clinical significance in glomerular disease is unknown. We investigated whether the polymorphisms of C-509T and T869C in TGF-beta1 account for interindividual variation in manifestations of IgA nephropathy (IgAN) using 626 Japanese subjects including 329 patients with histologically proven IgAN and 297 healthy controls with normal urinalysis. The frequencies of genotypes, alleles, and major haplotypes were similar between the patients and controls. The C-509T and T869C polymorphisms were in tight linkage disequilibrium, and the major haplotypes were C-C and T-T, which accounted for more than 95% of the total. In patients with -509CC and in those with the 869CC, urinary protein excretion was higher than in those with other genotypes, whereas no difference in other clinical manifestations was noted. Moreover, patients with -509CC and those with 869CC genotypes presented with a significant higher score of mesangial cell proliferation than in those with other genotypes. These results suggest that TGF-beta1 gene polymorphisms are specifically associated with heavy proteinuria and mesangial cell proliferation in Japanese patients with IgAN, although they do not confer susceptibility to this disease.