Quantifying comorbidity in peritoneal dialysis patients and its relationship to other predictors of survival.

BACKGROUND: Comorbidity is the single most important determinant of outcome in patients on renal replacement therapy. The aims of this study were to evaluate a semi-quantitative approach to comorbidity scoring in predicting survival of patients commencing peritoneal dialysis (PD), and to establish the interaction between this and other known predictors of patient outcome, in particular membrane function, residual renal function (RRF) and plasma albumin. METHODS: Comorbidity was recorded in a prospective, single centre cohort study of 303 patients commencing on PD. Using seven disease domains, chosen to reflect the dominance of cardiovascular morbidity in the end-stage renal failure population, comorbidity was graded as '0' when absent, '1' when one or two, and '2' when three or more conditions were present. The Wright comorbidity index, which includes age within the scoring method, was also evaluated. RRF, plasma albumin and peritoneal solute transport were measured every 6 months. Patients were censored at death. RESULTS: Median survival according to grade of comorbidity was 105, 42 and 29 months, respectively (P<0.0001), with good separation of the actuarial survival curves. Using Cox regression, the addition of age and the grade of comorbidity to Kt/V(urea), solute transport and plasma albumin increased the predictive power of the model. All were independent predictors of outcome with the exception of albumin. The Wright comorbidity index also enhanced the Cox model, although was not as powerful as when age and comorbidity were considered independently. At baseline, RRF was not different according to comorbidity unless diabetes was considered separately. Diabetics started with higher RRF, but after 6 months on PD this was the same as non-diabetic patients. Otherwise, initial rate of decline of RRF was similar across the comorbid grades, although the impact of higher drop-out due to earlier loss in patients with more comorbidity may have disguised earlier loss in these patients. Peritoneal solute transport tended to be higher in patients with increased comorbidity at baseline, chi(2) 13.8, P=0.032, and this was sustained with time on treatment. CONCLUSION: Comorbidity has a quantitative effect on survival that is independent of age, RRF and membrane function in PD patients. Comorbidity also appears to be associated with increased solute transport at the start of treatment, which is sustained. With the exception of diabetes, grade of comorbidity does not have a profound effect on loss of RRF.

Solitary functioning kidney and diverse genital tract malformations associated with hepatocyte nuclear factor-1beta mutations.

BACKGROUND: Renal tract malformations are, on occasion, associated with uterine malformations. The transcription factor hepatocyte nuclear factor (HNF)-1beta is expressed from the earliest stages of development of the Wolffian duct, the mesonephros and metanephros, and the Müllerian ducts in the mouse. In adult mice HNF-1beta is expressed in the kidney tubules, collecting ducts, and in the oviducts and uterus in the female (Müllerian duct derivatives) and in the epididymis, vas deferens and seminal vesicles (Wolffian duct derivatives) in the male. HNF-1beta mutations have been reported in two families where affected members have renal abnormalities, female genital tract malformations and early-onset diabetes. Renal and uterine abnormalities have not been described in families without early-onset diabetes. METHODS: We sequenced the HNF-1beta gene in nine subjects with renal abnormalities and a personal or family history of female genital tract malformations, but no history of diabetes. RESULTS: Two families were identified with novel HNF-1beta mutations: a missense mutation in exon 2 with conversion of serine to proline at codon 151 (S151P) and a frameshift mutation in exon 3 with a 1 base pair deletion at codon 243 (Q243fsdelC). The S151P mutation proband has cystic kidneys and uterus didelphys. Her affected second son has renal cysts and hypospadias. The Q243fsdelC proband has a single functioning kidney and her two children have renal dysplasia. Histology in one child shows cystic dysplasia with a lack of glomeruli. The proband's sister is a mutation carrier and has a bicornuate uterus. Diabetes is not a feature in either family. CONCLUSIONS: This study confirms an association between HNF-1beta mutations and renal and Müllerian anomalies. The hypospadias may be coincidental. This study describes the first HNF-1beta mutations that are associated with a single functioning kidney and the absence of diabetes. This study further reinforces the variability of the renal and non-renal phenotypes associated with HNF-1beta mutations.

Peritoneal glucose exposure and changes in membrane solute transport with time on peritoneal dialysis.

Peritoneal solute transport increases with time on treatment in a proportion of peritoneal dialysis (PD) patients, contributing to ultrafiltration failure. Continuous exposure of the peritoneum to hypertonic glucose solutions results in morphologic damage that may have a causative role in changes in peritoneal function. The purpose of this analysis was to establish whether increased exposure to glucose preceded changes in solute transport in a selected group of long-term PD patients. Peritoneal solute transport, residual renal function, peritonitis rate, and peritoneal exposure to glucose were recorded prospectively in a cohort of 303 patients at a single dialysis center. A subgroup of individuals, treated continuously for 5 yr, were identified and defined retrospectively as having either stable or increasing transport status. Of the 22 patients who were treated continuously for 5 yr, 13 had stable solute transport (solute transport at start, 0.67 [+/-0.1]; at 5 yr, 0.67 [+/-0.1]), whereas 9 had a sustained increase (solute transport at start, 0.56 [+/-0.08]; at 5 yr, 0.77 [+/-0.09]). Compared with the stable patients, those with increasing transport had earlier loss in residual renal function and were exposed to significantly more hypertonic glucose during the first 2 yr of treatment that preceded the increase in solute transport. This was associated with greater achieved ultrafiltration compensating for the reduced urinary volumes in these patients. Further increases in glucose exposure were observed as solute transport continued to rise. Peritonitis, including severity of infection and causative organism, was similar in both groups. In this selected group of long-term survivors on PD, an increase in solute transport with time was preceded by increased peritoneal exposure to hypertonic glucose. This is supportive evidence that hypertonic glucose may play a causative role in alterations in peritoneal membrane function.