Estimating the glomerular filtration rate in pregnancy: The evaluation of the Nanra and CKD-EPI serum creatinine-based equations.

AIM: To compare the performance of the Nanra and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimating glomerular filtration rate in pregnancy against the 24 h urine creatinine clearance. METHODS: Pregnant women had 24 h urine collections with simultaneous serum creatinine levels. Measured 24 h urine creatinine clearance was compared to two equations: Nanra and CKD-EPI. Level of concordance was measured, with an a priori bias acceptance of ±15 ml/min/1.73 m2. RESULTS: A total of 53 synchronous urine and serum creatinine samples were analysed. The Nanra equation had a bias of -13.4 ml/min/1.73 m2 while the CKD-EPI equation had bias of 14.2 ml/min/1.73 m2. Both equations showed a high degree of proportional error and had poor agreement with 24 h urine creatinine clearance. CONCLUSIONS: None of the equations were shown to reliably measure the estimated glomerular filtration rate in pregnant women. A valid serum creatinine-based estimated glomerular filtration rate equation in pregnancy is yet to be established.

A female with X-linked Alport syndrome and compound heterozygous COL4A5 mutations.

BACKGROUND: Female subjects with X-linked Alport syndrome have a single COL4A5 mutation, germ cell mosaicism in affected tissues and typically develop renal failure later or less often than male subjects. Women with two mutations are exceedingly rare, and usually have consanguineous parents or uniparental disomy. We describe here a 20-year-old woman who inherited two different COL4A5 variants, one from her father (c.2677G>C) and one from her mother (c.384 +1 G>A). CASE-DIAGNOSIS/TREATMENT: The index case had normal renal function, proteinuria and no clinically detectable hearing loss, or ocular abnormalities. Her father and paternal uncle developed end-stage renal disease at 37 and 28 years respectively, together with hearing loss, but not lenticonus or central retinopathy. Her mother had mildly impaired renal function, proteinuria, hearing loss, but no ocular abnormalities. Her maternal grandfather and 22-year-old brother, both with this mutation, developed renal failure by 28 years with hearing loss, or had proteinuria and hearing loss respectively. CONCLUSION: The index case has clinical features consistent with germ cell mosaicism of two COL45A mutations associated with adult-onset renal failure, but no ocular abnormalities. Her risk of renal failure is high, but the rate of progression to end-stage disease depends on the underlying mutations, and disease modification with renin-angiotensin blockade.

Potential roles of erythropoietin in the management of anaemia and other complications diabetes.

Erythropoietin (EPO) is a haematopoietic cytokine, mainly generated in the renal cortex, and its secretion and action is impaired in chronic kidney disease (CKD). Early renal damage in diabetes mellitus (DM) is usually not detected because diabetes-induced nephron hypertrophy maintains glomerular filtration rate (GFR) and an elevated plasma creatinine concentration is a relatively late manifestation of diabetic nephropathy. However, anaemia occurs more frequently in subjects with DM when compared with those with non-DM renal disease. While reduced production and a blunted response to EPO occurs in DM with early renal damage, other factors including chronic inflammation, autonomic neuropathy and iron deficiency are also important. Although recombinant human erythropoietin (rhEPO) has been an effective therapeutic agent in CKD anaemia, it appears to be more effective in patients with DM, even in earlier stages. Nevertheless, patients with DM are also more likely to be iron deficient, a barrier to effective rhEPO therapy. The effect of treatment on the reliability of haemoglobin A(1c) as an index of glycaemic control must be remembered. It is proposed that anaemia and its causes must be important components of care in subjects with early diabetic renal damage.

Haemodialysis-unresponsive blood pressure: cardiovascular mortality predictor?

AIM: The importance of 'conventional' cardiovascular risk factors in haemodialysis (HD) patients has been questioned following evidence that pre-HD blood pressure (BP) might be inversely related to mortality in contrast to post-HD BP. To evaluate this reverse BP epidemiology in HD patients, HD-induced BP changes were compared with aortic pulse wave velocity (PWV), an independent predictor of cardiovascular mortality. METHOD: Aortic PWV was evaluated in a limited care HD cohort, all of whom were asymptomatic of cardiovascular disease. RESULTS: Of 47 limited care patients, 45% were classified as HD responsive, with a 17% fall in mean arterial pressure compared with a 6% increase in the HD-unresponsive group. While there were no significant differences between the two groups in traditional vascular disease risk factors or interdialytic weight loss, PWV was significantly elevated in the HD-unresponsive group (12.9 +/- 2.7 compared with 10.8 +/- 2.9; P < 0.05). Furthermore, there was a positive correlation between the change in BP during HD and PWV in all subjects (r = 0.500; P < 0.001 for systolic blood pressure (SBP), a correlation that also existed for diastolic blood pressure (DBP) (P < 0.01). CONCLUSION: This study suggests that patients with HD-unresponsive BP are more likely to have vascular disease and this association between PWV and HD-induced BP changes might partly explain the apparent paradox of pre- and post-HD BP with mortality. It is proposed that a population with elevated post-HD BP is more likely to be composed of subjects with vascular disease (overt or occult), in contrast to a group with high pre-HD BP, which will be more heterogeneous.

Acute effect of haemodialysis on arterial stiffness: membrane bioincompatibility?

BACKGROUND: Repetitive endothelial damage from dialysis membrane incompatibility is a probable cause of accelerated atherosclerosis in haemodialysis patients. Consequently pulse wave velocity (PWV), a measure of arterial stiffness, was utilized as a surrogate marker of vascular dysfunction during dialysis with two commonly used synthetic dialysers. METHODS: PWV was monitored before, during and after haemodialysis using both polysulphone and polyamide membranes. PWV, an arterial stiffness measure, was calculated from the carotid to the femoral (C-F) and also to the radial (C-R) artery. In a further group, PWV was monitored while polysulphone and polyamide membranes were perfused with blood without dialysate. RESULTS: Mean aortic (C-F) PWV was lower during dialysis with the polyamide membrane, being 14 and 16% less following 75 and 135 min of dialysis (P<0.05) in 24 patients. Because intradialytic intravascular volume changes alter PWV, a subgroup analysis in 11 patients where dialysis fluid removal during both periods was minimal (<1 kg) was performed, and a persistent and significant increase in aortic PWV was detected with the polysulphone kidney being maximal (40%) at 75 min (P<0.01). This increase was negatively correlated with pre-dialysis PWV (P<0.01). In contrast, the polyamide dialyser did not change PWV. An increase in C-R PWV was also noted with the polysulphone membrane (P<0.05). In the nine patients where membranes were perfused with blood without dialysate, aortic PWV was again significantly increased by the polysulphone (P<0.01), but not the polyamide dialyser. CONCLUSIONS: Haemodialysis with polysulphone but not polyamide membranes acutely alters aortic 'stiffness', an effect postulated to be due to membrane bioincompatibility. However, factors including age, time on dialysis and underlying vascular disease, were also found to impact on these acute dialysis-induced changes to vascular function. Since these acute changes disappear post-dialysis, their long-term consequences are uncertain.