Tolvaptan in patients with autosomal dominant polycystic kidney disease

The course of autosomal dominant polycystic kidney disease (ADPKD) is often associated with pain, hypertension, and kidney failure. Preclinical studies indicated that vasopressin V(2)-receptor antagonists inhibit cyst growth and slow the decline of kidney function.

Association of functional haem oxygenase-1 gene promoter polymorphism with polycystic kidney disease and IgA nephropathy

Background: Haem oxygenase-1 (HO-1) is a cytoprotective molecule that is reported to have a protective role in a variety of experimental models of renal injury. A functional dinucleotide repeat (GT)n polymorphism, within the HO-1 promoter, regulates HO-1 gene expression; a short number of repeats (S-allele <25) increases transcription. We report the first assessment of the role of this HO-1 gene promoter polymorphism in chronic kidney disease due to autosomal dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IgAN).

Methods: The DNA from 160 patients (99% Caucasian) on renal replacement therapy (RRT) was genotyped. The primary renal disease was ADPKD in 100 patients and biopsy-proven IgAN in 60 patients.

Results: Overall, the mean age at commencement of RRT was not significantly different between patients with and without an S-allele (44.1 years versus 45.0 years, P = 0.64). In patients with ADPKD, the age at commencement of RRT was comparable regardless of the HO-1 genotype (47.7 years versus 46.7 years, P = 0.59). The same was true in patients with IgAN (38.3 years versus 42.2 years, P = 0.28).

Conclusion: This suggests that the functional HO-1 promoter polymorphism does not influence renal survival in CKD due to ADPKD or IgAN.

Optimising the management of polycystic kidney disease

Polycystic kidney disease (PKD) is the most common inherited renal disorder that results in chronic kidney disease. Clinical features include visible haematuria, loin pain, UTI and hypertension. The typical clinical course is a progressive increase in the number and size of renal cysts associated with gradual loss of kidney function (falling eGFR).

Incidence, determinants and outcome of chronic kidney disease after adult heart transplantation in the United Kingdom

Background: We investigated the incidence of chronic kidney disease (CKD) in the United Kingdom heart transplant population, identified risk factors for the development of CKD, and assessed the impact of CKD on subsequent survival.

Methods: Data from the UK Cardiothoracic Transplant Audit and UK Renal Registry were linked for 1732 adult heart transplantations, 1996 to 2007. Factors influencing time to CKD, defined as National Kidney Foundation CKD stage 4 or 5 or preemptive kidney transplantation, were identified using a Cox proportional hazards model. The effects of distinct CKD stages on survival were evaluated using time-dependent covariates.

Results: A total of 3% of patients had CKD at transplantation, 11% at 1-year and more than 15% at 6 years posttransplantation and beyond. Earlier transplantations, shorter ischemia times, female, older, hepatitis C virus positive, and diabetic recipients were at increased risk of developing CKD, along with those with impaired renal function pretransplantation or early posttransplantation. Significant differences between transplantation centers were also observed. The risk of death was significantly higher for patients at CKD stage 4, stage 5 (excluding dialysis), or on dialysis, compared with equivalent patients surviving to the same time point with CKD stage 3 or lower (hazard ratios of 1.66, 8.54, and 4.07, respectively).

Conclusions: CKD is a common complication of heart transplantation in the UK, and several risk factors identified in other studies are also relevant in this population. By linking national heart transplantation and renal data, we have determined the impact of CKD stage and dialysis treatment on subsequent survival in heart transplant recipients.

The continuous erythropoietin receptor activator (C.E.R.A.) corrects anemia at extended administration intervals in patients with chronic kidney disease not on dialysis:results of a phase II study

This study was designed to assess the potential of the continuous erythropoietin receptor activator (C.E.R.A.) to correct anemia at extended administration intervals in erythropoiesis-stimulating agent-naīve patients with chronic kidney disease (CKD) not on dialysis and to determine its optimal starting dose.

The practical implications of using standardized estimation equations in calculating the prevalence of chronic kidney disease

Background. Kidney Disease Outcomes Quality Initiative (KDOQI) chronic kidney disease (CKD) guidelines have focused on the utility of using the modified four-variable MDRD equation (now traceable by isotope dilution mass spectrometry IDMS) in calculating estimated glomerular filtration rates (eGFRs). This study assesses the practical implications of eGFR correction equations on the range of creatinine assays currently used in the UK and further investigates the effect of these equations on the calculated prevalence of CKD in one UK region Methods. Using simulation, a range of creatinine data (30–300 µmol/l) was generated for male and female patients aged 20–100 years. The maximum differences between the IDMS and MDRD equations for all 14 UK laboratory techniques for serum creatinine measurement were explored with an average of individual eGFRs calculated according to MDRD and IDMS 30 ml/min/1.73 m2. Observed data for 93,870 patients yielded a first MDRD eGFR 3 months later of which 47 093 (71%) continued to have an eGFR

Regulation and consequences of differential gene expression in diabetic kidney disease

DIN (diabetic nephropathy) is the leading cause of end-stage renal disease worldwide and develops in 25-40% of patients with Type 1 or Type 2 diabetes mellitus. Elevated blood glucose over long periods together with glomerular hypertension leads to progressive glomerulosclerosis and tubulointerstitial fibrosis in susceptible individuals. Central to the pathology of DIN are cytokines and growth factors such as TGF-beta (transforming growth factor beta) superfamily members, including BMPs (bone morphogenetic protein) and TGF-beta 1, which play key roles in fibrogenic responses of the kidney, including podocyte loss, mesangial cell hypertrophy, matrix accumulation and tubulointerstitial fibrosis. Many of these responses can be mimicked in in vitro models of cells cultured in high glucose. We have applied differential gene expression technologies to identify novel genes expressed in in vitro and in vivo models of DN and, importantly, in human renal tissue. By mining these datasets and probing the regulation of expression and actions of specific molecules, we have identified novel roles for molecules such as Gremlin, IHG-1 (induced in high glucose-1) and CTGF (connective tissue growth factor) in DIN and potential regulators of their bioactions.

The Effects of Anti-Hypertensive Drugs Evaluated Using Markov Modelling for Northern Ireland Chronic Kidney Disease Patients

The aim of this paper is to use Markov modelling to
investigate survival for particular types of kidney patients
in relation to their exposure to anti-hypertensive treatment
drugs. In order to monitor kidney function an intuitive three
point assessment is proposed through the collection of blood
samples in relation to Chronic Kidney Disease for Northern
Ireland patients. A five state Markov Model was devised
using specific transition probabilities for males and
females over all age groups. These transition probabilities
were then adjusted appropriately using relative risk scores
for the event death for different subgroups of patients. The
model was built using TreeAge software package in order to
explore the effects of anti-hypertensive drugs on patients.