Anticipation of end stage renal disease in patients with autosomal dominant polycystic kidney disease in successive generations.

Autosomal dominant polycystic kidney disease is a disorder, which is inherited in 50% of offspring, irrelevant the sex and it has a variable clinical expressivity. Initially it was noticed that the clinical expression was interfamilial, but some studies found out that it was different. The aim of this study was to evaluate the age of onset of end-stage renal disease (ESRD) in affected parents in comparison with their offspring in successive generations. We studied 60 families of patients with autosomal dominant polycystic kidney disease (ADPKD). The diagnosis was done by echo criteria and we included only the patients for whom we knew precisely the onset of ESRD (affected parent and offspring), the sex of the parent who suffered from the disease, and offspring. We found out that the ESRD in ADPKD appears at the same age in affected parents and offspring (49,3 +/- 7,9 Vs 51,8 +/- 9,2, p = NS) irrelevant of the sex of the offspring. Patients with paternal inheritance (n = 38) were diagnosed to have ESRD earlier than their affected parents (47,9 +/- 8,3 Vs 52,2 +/- 9,2 p < 0,05), but patients with maternal inheritance had no difference (n = 22) (51,9 +/- 6,8 Vs 51,2 +/- 9,4, p = NS). In all the patients (60 couples) the survival rate was the same between affected parents and offspring (p = NS, Kaplan-Meier test), but significant differences were noticed between offspring with paternal inheritance in comparison with their parents (p < 0,05). In conclusion, we have detected that the onset of ESRD between patients with ADPKD in successive generations: a) Occurs in offspring as in their ancestors, b) anticipation was observed in 55% of couples, c) the sex of offspring does not have any relation with the renal death and d) the ESRD in patients with paternal inheritance occurs earlier in offspring than in their ancestors but not with maternal.     

The Influence of the Endothelin-Converting Enzyme-1 Gene Polymorphism on the Progression of Autosomal Dominant Polycystic Kidney Disease

Background. A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD), the most common renal hereditary disease. Endothelin-1 (ET-1) has been suggested to be an important disease-promoting factor of the kidney. Endothelin-converting enzyme-1 (ECE-1) is the main protease responsible for ET-1 generation by cleavage of its functionally inactive precursor. We examined the influence of the ECE-1b C-338A polymorphism on the progression of ADPKD toward end-stage renal disease (ESRD). The A allele was suggested to be associated with higher plasma level of ET-1. Methods. 200 ADPKD patients (107 males, 93 females) who had reached ESRD were analyzed. Patients were divided into three groups: (1) 47 patients (23 males, 24 females) with ESRD later than in 63 yr (slow progressors); (2) 71 patients (38 males, 33 females) with ESRD before 45 yr (rapid progressors); and (3) 82 patients (46 males, 36 females) with ESRD between 45–63 yr. Moreover, we analyzed 160 genetically unrelated healthy Czech subjects as the control group (82 males, 78 females, mean age 51.4 ± 8.2 yr). DNA samples from collected blood were genotyped for ECE-1b C-338A polymorphism using described polymerase chain reaction (PCR) followed by restriction enzyme digestion. We compared the frequencies of different genotypes between the groups of slow and rapid progressors and the ages of ESRD with regard to different genotypes. Results. The ECE-1b C-338A genotype distribution showed no differences among the groups of slow progressors, rapid progressors, ADPKD group with ESRD between 45–63 yr and control group. Comparing the ages of ESRD of all patients, we did not find significant differences in the ages with regard to different genotypes: CC (51.5 ± 10.1 yr), AC (51.6 ± 11.4 yr), AA (48.2 ± 5.9 yr). There was a tendency to lower age of ESRD in AA homozygotes in comparison with other genotypes (t-test, p = 0.12). We found no influence of gender. Conclusion. We excluded the effect of ECE-1b C-338A polymorphism on the progression of ADPKD. We could observe a mild tendency toward faster decline of renal function in AA homozygous individuals.     

Differences in new-onset IgA nephropathy between young adults and the elderly

Background: The goal of this study was to define the clinical and histological differences in new-onset IgA nephropathy between young adults and the elderly. Methods: We retrospectively examined renal biopsy findings, clinical features at presentation and outcomes in 82 young adults (mean age 30.3 ± 10.2 years) and 17 elderly patients (mean age 71.9 ± 4.5 years) with IgA nephropathy whose renal biopsies were taken within 1 year from the onset of renal manifestations. Results: The elderly group more frequently had hypertension (p < 0.001), acute renal failure (p < 0.001), and nephrotic range proteinuria (p = 0.001) at presentation than the young adults group. On histology, a higher percentage of globally sclerotic glomeruli (p < 0.001) was present in the elderly group. In patients presenting with acute renal failure, the elderly group more frequently had an intercurrent disease (p = 0.02), mostly infection, and a higher mortality rate (p = 0.033). On histology, the young adults group had a higher percentage of glomeruli affected by crescents (p = 0.027); in contrast, the elderly group more commonly had acute tubular injury (p = 0.02). Conclusions: The elderly patients affected by IgA nephropathy had more severe renal manifestations at presentation (acute renal failure in 52.9% and nephrotic syndrome in 41.2% of patients). In cases of acute renal failure, the elderly patients had more predominant tubular rather than glomerular injury. Moreover, the considerable mortality rate (44.4%) might be associated with the intercurrent disease, mostly infection, which was more commonly present in the elderly patients.     

The Relationship between Oxidative Stress,Inflammation, and Atherosclerosis in Renal Transplant and End-Stage Renal Disease Patients

Objectives: Cardiovascular risk is increased in the early stages of chronic kidney disease (CKD) and is also found to be ongoing in renal transplant (Rtx) patients. As a sign of atherosclerosis, increased carotid intima–media thickness (CIMT) has been widely accepted as a strong predictor of cardiovascular disease (CVD) and mortality in the end-stage renal disease (ESRD) patients. Ischemia-modified albumin (IMA), pentraxin-3 (PTX-3), and neutrophil-to-lymphocyte ratio (NLR) were introduced as oxidative stress and inflammatory biomarkers in ESRD. The role of Rtx in terms of atherogenesis, oxidative stress, and inflammation is still unclear. We aimed to investigate the relationship between IMA, PTX-3, NLR, and CIMT in Rtx patients without overt CVD and to compare these results with those obtained from healthy subjects and ESRD patients receiving hemodialysis (HD) and peritoneal dialysis (PD). Design and methods: Cross-sectional analysis in which CIMT measurements, NLR, and serum PTX-3 and IMA levels were assessed in 18 Rtx patients (10 females; mean age: 40.0 ± 13.3 years), 16 PD patients (7 females; 40.2 ± 12.9 years), 14 HD patients (8 females; 46.6 ± 10.7 years), and 19 healthy subjects (9 females; 36.9 ± 8.9 years). Results: IMA, PTX-3, and high-sensitive C-reactive protein (hs-CRP) levels, NLR, and CIMT of Rtx patients were found to be significantly higher compared with healthy subjects (?p = 0.04, p < 0.0001, p < 0.005, p = 0.005, and p = 0.005, respectively). IMA level was positively correlated with hs-CRP and PTX-3 levels, NLR, and CIMT when all participants were included (r = 0.338, p = 0.005; r = 0.485, p < 0.0001; r = 0.304, p = 0.013; and r = 0.499, p < 0.0001, respectively). Conclusion: There has been ongoing inflammation, oxidative stress, and atherosclerosis in Rtx patients.     

The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.     

Effect of Hemodialysis on Cognitive Function in ESRD Patients

Background. Uremia is associated with impairment of different cognitive functions. However the pathogenesis of this cognitive dysfunction is unknown. Objective. In this study, long-latency event related potentials (ERPs) were used to assess changes in cortical function due to hemodialysis treatment. Methods. In this cross-sectional study, we measured event related potentials in 15 end stage renal disease (ESRD) patients maintained on hemodialysis, two hours before and two hours after they underwent hemodialysis and compared their data with a strictly age and sex matched healthy control group. The P3 was elicited by using standard auditory “odd-ball” paradigm and the data obtained was statistically analyzed (Wilcoxon signed ranks, Mann Whitney). Results. Before hemodialysis, the patients' P3 latency (347.73 ± 39.47 ms) was significantly increased as compared with that of healthy control group (308.4 ± 13.73 ms) (p = 0.001). After hemodialysis, P3 latency of the patients showed a significant decrease (347.73 ± 39.47 ms to 325.20 ± 37.15 ms, p = 0.001). P3 latency after dialysis was not significantly different from controls. No significant correlation was noted between various biochemical parameters (hemoglobin, blood urea, creatinine, uric acid and calcium) and P3 latency or amplitude. Conclusions. Removal of uremic toxins by hemodialysis leads to an improvement in cognitive processing.     

The role of parental hypertension in the frequency and age of diagnosis of hypertension in offspring with autosomal-dominant polycystic kidney disease

BACKGROUND: Hypertension in autosomal-dominant polycystic kidney disease (ADPKD) patients is associated with more rapid progression of renal disease and a high incidence of left ventricular hypertrophy (LVH). The present study was undertaken to examine the role of parental hypertension in the occurrence of hypertension in 475 ADPKD offspring. METHODS: Adult subjects participating in an ongoing study of the natural history of ADPKD were included in the analysis if they were diagnosed with ADPKD, had a known affected parent, and knew the hypertensive status of both parents. RESULTS: When the affected parent was hypertensive, the ADPKD male (82% versus 62%, P < 0.05) and female (61% versus 37%, P < 0.005) offspring had a significantly higher frequency of hypertension than when the ADPKD-affected parent was normotensive. The median age of diagnosis of hypertension was also significantly earlier in both male (33 years versus 40 years, P < 0.05) and female (38 years versus 50 years, P < 0.05) ADPKD patients when their affected parents were hypertensive as compared with normotensive. These effects of hypertension in the affected parent on hypertension in the ADPKD offspring were independent of age, renal volume, and renal function in the offspring. Hypertension in unaffected parents also increased the frequency of hypertension in the ADPKD female (69% versus 53%, P < 0.01), but not male (89% versus 77%, NS) subjects. CONCLUSION: The results indicate that parental hypertension influences the frequency of hypertension in ADPKD patients.     

Ambulatory Blood Pressure and Endothelial Dysfunction in Patients with Autosomal Dominant Polycystic Kidney Disease

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. However, the association between ambulatory blood pressure and ED has not been investigated in these patients. Forty-one patients with ADPKD having well-preserved renal function were included in the study. Ambulatory blood pressure monitoring was performed in all patients. Patients were divided into dipper and non-dipper groups. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. The mean 24-hour systolic blood pressure was similar in both groups (125.5 ± 10.7 mmHg in dippers and 121.2 ± 14.3 in non-dippers, p > 0.05). There was also no significant difference between the mean 24-hour diastolic blood pressures in both groups (82.3 ± 9.6 mmHg in dippers and 77.1 ± 8.6 mmHg in non-dippers, p > 0.05). The nocturnal fall rate in systolic blood pressure was 11.1 ± 1.2% in dippers and 0.98 ± 0.9% in non-dippers (p = 0.001). The nocturnal fall rate in diastolic blood pressure was 14.0 ± 0.9% in dippers and 3.8 ± 0.8% in non-dippers (p = 0.001). Endothelial-dependent dilatation was significantly higher in dippers compared to non-dippers (6.22 ± 4.14% versus 3.57 ± 2.52%, p = 0.025). Non-dipper patients with ADPKD show significant ED, which has an important impact on cardiovascular morbidity and mortality.     

Relationship between GSTs Gene Polymorphism and Susceptibility to End Stage Renal Disease among North Indians

Background and Objective. Glutathione-S-transferase (GST) is the superfamily of genes that provides protection to the cells against reactive oxygen species and plays a vital role in phase II of biotransformation of many substances. Overexpression of GST (EC 2.5.1.18) has been documented in the erythrocytes of patients with chronic renal failure, which may be of clinical relevance. Keeping this background in mind, we have investigated the relationship between human GST gene polymorphism in end stage renal disease (ESRD) patients. Design and Methods. We have assessed 184 patients with ESRD and 569 age-and sex-matched controls from North India. The GSTT1 and GSTM1 null genotypes were identified by polymerase chain reaction (PCR). GSTP1–313 A/G mutation was determined by PCR followed by restriction enzyme digestion. Results. The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphism were evaluated. We observed that GSTM1 null genotype was present in 46.74% of the ESRD patients while GSTT1 null genotype was present in 58.7% of the ESRD subjects. The genotypic distribution of GSTP1 was Ile₁₀₅/Ile₁₀₅ in 47.3%, Ile₁₀₅/Val₁₀₅ in 30.97% and Val₁₀₅/Val₁₀₅ in 21.74% of ESRD patients. There was a significant association of null alleles of the GSTM1 (p = 0.0386; OR = 1.445, 95% CI = 1.033–2.021) and GSTT1 (p ≤ 0.0001; OR = 4.568, 95% CI = 3.215–6.492) and in the -313 G alleles (Val) of the GSTP1 gene (p = 0.0032; OR = 1.956, 95% CI = 1.265–3.024) with end stage renal disease. The combined analysis of the three genotypes showed a further increased risk to ESRD (p ≤ 0.0001; OR = 9.01, 95% CI = 5.55–14.626). Interpretations and Conclusions. The null / low polymorphism of the detoxifying enzymes GSTT1, GSTM1, and GSTP1 are associated with the risk of developing ESRD in North Indian patients.     

IONIZED SERUM CALCIUM LEVELS DURING ACUTE RENAL FAILURE: INTERMITTENT HEMODIALYSIS VS. CONTINUOUS HEMODIAFILTRATION

Background: Achieving “adequacy of dialysis” includes the maintenance of normal serum ionized calcium concentrations and is an important therapeutic goal in the treatment of acute renal failure (ARF). It is unknown whether this goal is best achieved with intermittent or continuous renal replacement therapy. Methods: We compared the effects of continuous veno–venous hemodiafiltration (CVVHDF) and intermittent hemodialysis (IHD) on serum ionized calcium concentrations using daily morning blood tests in 88 consecutive intensive care patients of which half were treated with IHD and half with CRRT. Results: Mean patient age was 54 ± 14 years for IHD and 60 ± 14 years for CVVHDF (NS). However, patients who received CVVHDF were significantly more critically ill (mean APACHE II scores: 24.4 ± 5.1 for IHD vs. 29.2 ± 5.7 for CVVHDF, p<0.003). Before treatment, the mean ionized calcium concentration was 1.177 ± 0.03 mmol/l for IHD and 1.172 ± 0.04 mmol/l for CVVHDF (NS), with abnormal values in 51.6% of IHD patients and in 68% of CVVHDF patients (NS). During treatment, hypocalcemia was significantly more common among CVVHDF patients (24.5% vs. 14.9%; p<0.011) while hypercalcemia was more frequent during IHD (36.1% vs. 25.6%; p<0.019). Conclusions: Abnormal serum ionized calcium concentrations are frequent in ARF patients before and during renal replacement. Once dialytic therapy is applied, CVVHDF is more likely to lower serum calcium concentrations, while IHD is more likely to induce hypercalcemia. Appreciation of these different biochemical effects may assist clinicians in adjusting dialytic therapy in selected patients.     

INFLUENCE OF THE ENDOTHELIAL NITRIC OXIDE SYNTHASE POLYMORPHISM ON THE PROGRESSION OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE AND IgA NEPHROPATHY

Background: The reason of variability of clinical course and progression to end-stage renal failure (ESRF) of two widespread chronic nephropathies—autosomal dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IGAN) is not clear. The endothelial dysfunction is considered in the number of factors possibly influencing the prognosis of these nephropathies. Our study tried to verify the hypothesis that endothelial nitric oxide synthase (ecNOS) gene polymorphisms in intron 4 could have some relevance to the progression of ADPKD and/or IgA nephropathy. Methods: We examined 128 Czech patients with ADPKD (62 males, 66 females) and 93 patients with IGAN (51 males, 42 females). As a control group, we used 100 genetically unrelated healthy subjects (50 men, 50 women, mean age 51.2 ± 8.2). The genomic DNA was amplified by polymerase chain reaction (PCR) and the products were separated on 1.5% agarose gel and visualized by ultraviolet transillumination. We compared homozygous subjects for ecNOSb allele with homozygous and heterozygous subjects for ecNOSa allele. Results: The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 19% (19/100) and 81% (81/100) in the control group. The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes in ADPKD patients were: 26.6% (8/30) and 73.4% (22/30) in ADPKD patients with normal renal function, 30% (9/30) and 70% (21/30) in ADPKD with ESRF, 35.2% (18/51) and 64.8% (33/51) in young ADPKD patients, 60% (12/20) and 40% (8/20) in ADPKD patients with ESRF later than in 62 years. In IGAN, the frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 24% (12/50) and 76% (38/50) in IgA with normal renal function and 20.9% (9/43) and 79.1% (38/43) in IgA with ESRF. Conclusion: Both in ADPKD and IGAN groups, there was no significant difference in the frequencies of ecNOS genotypes between patients with normal renal function and age matched patients with ESRF and between patients with normal renal function and control group. The frequency of ecNOSa allele was significantly higher in a number limited group ADPKD patients with ESRF later than in 62 years (Chi-square test p<0.05). This higher frequency of a allele among ADPKD patients with later onset of ESRF could suggest the trend of positive influence of a allele in ADPKD patients.     

INFLUENCE OF THE ENDOTHELIAL NITRIC OXIDE SYNTHASE POLYMORPHISM ON THE PROGRESSION OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE AND IgA NEPHROPATHY

Background: The reason of variability of clinical course and progression to end-stage renal failure (ESRF) of two widespread chronic nephropathies–-autosomal dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IGAN) is not clear. The endothelial dysfunction is considered in the number of factors possibly influencing the prognosis of these nephropathies. Our study tried to verify the hypothesis that endothelial nitric oxide synthase (ecNOS) gene polymorphisms in intron 4 could have some relevance to the progression of ADPKD and/or IgA nephropathy. Methods: We examined 128 Czech patients with ADPKD (62 males, 66 females) and 93 patients with IGAN (51 males, 42 females). As a control group we used 100 genetically unrelated healthy subjects (50 men, 50 women, mean age 51.2 ± 8.2). The genomic DNA was amplified by polymerase chain reaction (PCR) and the products were separated on 1.5% agarose gel and visualized by ultraviolet transillumination. We compared homozygous subjects for ecNOSb allele with homozygous and heterozygous subjects for ecNOSa allele. Results: The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 19% (19/100) and 81% (81/100) in the control group. The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes in ADPKD patients were: 26.6% (8/30) and 73.4% (22/30) in ADPKD patients with normal renal function, 30% (9/30) and 70% (21/30) in ADPKD with ESRF, 35.2% (18/51) and 64.8% (33/51) in young ADPKD patients, 60% (12/20) and 40% (8/20) in ADPKD patients with ESRF later than in 62 years. In IGAN the frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 24% (12/50) and 76% (38/50) in IgA with normal renal function and 20.9 % (9/43) and 79.1% (38/43) in IgA with ESRF. Conclusion: Both in ADPKD and IGAN groups there was no significant difference in the frequencies of ecNOS genotypes between patients with normal renal function and age matched patients with ESRF and between patients with normal renal function and control group. The frequency of ecNOS a allele was significantly higher in a number limited group ADPKD patients with ESRF later than in 62 years (Chi-square test p < 0.05). This higher frequency of a allele among ADPKD patients with later onset of ESRF could suggest the trend of positive influence of a allele in ADPKD patients.     

Prevalence of malnutrition in Nigerians with chronic renal failure

In developed countries, malnutrition is common in patients with chronic renal failure (CRF) and has adverse effects on patient morbidity and mortality. The prevalence of malnutrition before the initiation of dialysis is poorly characterized in CRF patients in developing countries. We studied the prevalence of malnutrition among Nigerians with CRF before commencement of dialysis. Body mass index (BMI) and serum protein levels were measured in 74 dialysis naïve Nigerians with CRF and 48 controls. Patients with nephrotic syndrome, steroid use and failure of organs other than the kidneys were excluded. The mean BMI was significantly lower in the patients compared to the controls (22.4 ± 14.9 kg/M² Vs. 25.2 ± 2.7 kg/M²; p = 0.0001). Low BMI (less than 20 Kg/M²) was present in 16 (21.6%) of the patients compared with one of the controls. The mean serum total protein and albumin were also significantly lower in the patients compared to controls (61.9 ± 14.4 g/L Vs. 73.8 ± 6.8 g/L; p < 0.0001, and 31.5 ± 9.3 g/L Vs. 39.6 ± 4.4 g/L; p < 0.0001 respectively). Protein malnutrition (serum albumin < 29 g/L) was present in 32 (43.2%) of patients with CRF and one (2.1%) of the control subjects. Malnutrition is common in Nigerian CRF patients before the commencement of dialysis. In these patients, emphasis should be placed on prevention and/or correction of malnutrition because of its documented adverse effects on the outcomes of maintenance dialysis.     

The efficacy of low-dose tadalafil in patients undergoing hemodialysis with end-stage renal disease

Background: Erectile dysfunction (ED) is a disorder that is frequently observed in people with chronic kidney disease who undergo hemodialysis (HD). In the context of evidence-based medicine, we aimed to investigate the effect of low-dose tadalafil on sexual function in patients undergoing HD.

Methods: The medical records of 30 males (aged 29–65?years) with end-stage renal disease (ESRD) on a HD program, and who had received 5?mg tadalafil twice weekly, were retrospectively evaluated. Changes in erectile and ejaculatory function were evaluated using the International Erectile Function Index questionnaire, the Erection Hardness Scale (EHS), and the Male Sexual Health Questionnaire (MSHQ).

Results: The mean age of the patients was 47.6?±?10.1?years, their mean body mass index was 24.3?±?4.2?kg/m², their mean hemoglobin was 11.9?±?0.9?g/dL, and their mean creatinine clearance was 5.8?±?1.1?mL/min. At the third month of treatment, 36.6% of the patients had no ED, 40% had mild ED, 10% had mild-to-moderate ED, and 13.3% had moderate ED. The mean MSHQ scores (p?p?=?.001) were significantly improved. There was no significant difference between Beck's Depression Inventory scores (p?>?.05), but Hamilton anxiety rate scores decreased significantly (p?=?.001). The quality-of-life score improved throughout the study period (p?Conclusions: Tadalafil therapy is an effective therapeutic option in patients with ESRD who undergo HD, not only for the treatment of ED, but also for ejaculatory function, with acceptable adverse effects.     

THE INFLUENCE OF l-CARNITINE SUPPLEMENTATION ON HEMATOCRIT AND HEMOGLOBIN LEVELS IN PATIENTS WITH END STAGE RENAL FAILURE ON CAPD

The influence of l-carnitine supplementation on hematocrit (Hct) and hemoglobin (Hb) levels, in patients suffering from end stage renal disease (ESRD) on maintenance hemodialysis, are well known from several studies. The data concerning the serum levels of carnitine, in patients with ESRD on continuous ambulatory peritoneal dialysis (CAPD) are contradictory, but most of them support that they are rather normal. In this study the effect of l-carnitine supplementation on Hct, and Hb levels were investigated in patients suffering from ESRD on CAPD. In the study 12 patients were included (5 F, 7 M), aged from 39 to 92 years old (median 65.5 years), who were on CAPD for more than 6 months (from 6 to 15 months, mean ± SD = 8.6 ± 3.6), with normal serum ferrum and ferritin levels at the beginning of the study. Two grams of l-carnitine/day per os (Superamin, Vianex Hellas), were administered in all the patients and the serum ferrum levels were tried to be kept stable, by exogenous ferrum administration, during the study period. If the Hct levels were more than 36% per month the erythropoietin (rHuEpo) dose of the patient was decreased monthly at the half dose/week. The changes of Hct, Hb, ferrum and ferritin levels, as well as the Indice de Rigidite (IR) of the erythrocytes were recorded, before and after the first, second and third month of the study period. Finally, the rHuEpo dose/patient was registered monthly before and during the study. During the observations, Hct (35.4 ± 3.3 vs. 38.1 ± 3.4, ANOVA, p < 0.03) and Hb levels (11.0 ± 1.1 vs. 11.9 ± 1, ANOVA, p < 0.01), were significantly increased. On the other hand, rHuEpo dose necessity/patient/week was decreased significantly (3833 ± 3326 vs. 1292 ± 1712, ANOVA, p < 0.01), in order to succeed the target Hct level. Furthermore, red blood cells IR also appeared to have a significant decrease (16.6 ± 7.4 vs. 13.0 ± 3.9, paired t-test, p < 0.03). Finally, the ferrum and ferritin levels were stable during the study period. It was concluded, that in patients on, CAPD the per os l-carnitine supplementation decreased, the red blood cells IR which contributes to the: (a) Increase of Hct and Hb levels and (b) decrease of the patients rHuEpo dose/week.     

C REACTIVE PROTEIN IN PATIENTS WITH CHRONIC RENAL DISEASES

Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53 ± 5.8 years with a mean creatinine clearance (C_Cr) of 52 ± 37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0 ± 4.6 mg/L and 5.8 ± 5.6 pg/mL, respectively and were not significantly correlated (r = 0.11, p = n.s.). CRP and IL-6 were however related with renal function (CRP versus C_Cr r = ?0.40 p < 0.001; IL-6 versus C_Cr r = ?0.45; p < 0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4 ± 6.3 mg/L in the group of patients with a C_Cr lower than 20 mL/min (n = 32) and 2.76 ± 4.35 in the group of patients with a C_Cr higher than 20mL/min (n = 70) (p < 0.0001). CRP and IL-6 were positively related with ESR (r = 0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2 ± 0.4 versus 3.0 ± 0.5 g/dL). CRP and serum albumin were not significantly related (r = 0.17). CRP and IL-6 correlated positively with ESR (r = 0.32 and 0.46 respectively). In pre-dialysis patients we have demonstrated an increase in both CRP and IL-6 that occurs as renal function decreases. These data provided evidence of the activation – even in the predialysis phase of renal failure – of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.     

Chronic kidney disease care program improves quality of pre-end-stage renal disease care and reduces medical costs

Aim: Multidisciplinary care of patients with chronic kidney disease (CKD) provides better care outcomes. This study is to evaluate the effectiveness of a CKD care program on pre‐end‐stage renal disease (ESRD) care. Methods: One hundred and forty incident haemodialysis patients were classified into the CKD Care Group (n = 71) and the Nephrologist Care Group (n = 69) according to participation in the CKD care program before dialysis initiation. The ‘total observation period’ was divided into ‘6 months before dialysis’ and ‘at dialysis initiation’. Quality of pre‐ESRD care, service utilization and medical costs were evaluated and compared between groups. Results: The mean estimated glomerular filtration rates at dialysis initiation were low in both groups; but the levels of haematocrit and serum albumin of the CKD Care Group were significantly higher. The percentages of patients initiating dialysis with created vascular access, without insertion of double‐lumen catheter and without hospitalization were 57.7%, 50.7% and 40.8%, respectively, in the CKD Care Group, and 37.7%, 29.0% and 18.8% in the Nephrologist Care Group (P < 0.001). Participation in the CKD care program, though with higher costs during the 6 months before dialysis ($US1428 ± 2049 vs US$675 ± 962/patient, P < 0.001), was significantly associated with lower medical costs at dialysis initiation ($US942 ± 1941 vs $US2410 ± 2481/patient, P < 0.001) and for the total period of observation ($US2674 ± 2780 vs $US3872 ± 3270/patient, P = 0.009). The cost‐saving effect came through the early preparation of vascular access and the lack of hospitalization at dialysis initiation. Conclusion: CKD care programs significantly improve quality of pre‐ESRD care, decrease service utilization and save medical costs.     

CORONARY ARTERY DISEASE AMONG DIABETIC AND NON-DIABETIC PATIENTS WITH END STAGE RENAL DISEASE

Cardiovascular disease is the major cause of death among patients with end stage renal disease and accounts for about half the deaths among the dialysis population. Several researchers have reported a high prevalence of coronary artery disease among diabetic patients with renal failure and coronary arteriography is often considered an integral part of the pretransplant evaluation of diabetic patients with end stage renal disease. However, very few reports have addressed the question of coronary disease in non-diabetic patients, and the pattern and prevalence of coronary artery disease in non-diabetic patients with end stage renal disease are not well defined. We evaluated the clinical and coronary angiographic findings in 158 consecutive patients (84 diabetic and 74 non-diabetic) with end stage renal disease. The coronary arteries were divided into 16 segments and each segment was analyzed for the presence of coronary disease, which was defined as the presence of ≥ 50% luminal diameter stenosis. Diabetic patients had more adverse risk factors for coronary artery disease, yet there was no significant difference in the prevalence of coronary artery disease between the diabetic and non-diabetic patients (67% vs. 55%, p = 0.15), or in the number of affected coronary artery segments (2.0 vs. 1.4, p = 0.05). Triple vessel coronary artery disease was however, significantly more common among the diabetic subjects (27% vs. 12%, p = 0.005). Non-diabetic patients with end stage renal disease also have a high prevalence of coronary artery disease and may merit as careful investigation of their coronary status as their diabetic counterparts.     

Improvement of Endothelial Dysfunction with Simvastatin in Patients with Autosomal Dominant Polycystic Kidney Disease

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. Statins have a beneficial effect in the reversal of ED. The aim of this study was to investigate the effects of a statin, simvastatin, on ED in patients with ADPKD. Sixteen patients with ADPKD having well-preserved renal function were included in the study. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation (EDD) was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. After the baseline evaluations of EDDs, patients were started treatment with simvastatin at a dose of 40 mg/day and were treated for six months. EDDs were recalculated after one and six months of therapy. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were also measured as markers of inflammation. Baseline EDD was 11.3 ± 6.9% in patients with ADPKD. After one month of simvastatin treatment, EDD increased significantly to 14.6 ± 4.6 % (P = 0.016 versus baseline). Endothelial-dependent dilatation further increased significantly to 18.9 ± 7.5 % (P = 0.011 versus baseline, P = 0.048 versus first month) after six months of therapy. There was also a significant decrease in the level of IL-6 from 21.6 ± 21.7 pg/mL to 9.1 ± 3.5 pg/mL (P= 0.002).

Six months of simvastatin therapy resulted in a significant improvement of ED in patients with ADPKD. This finding may be in part related to the pleiotropic effects of simvastatin.