A comparison of the epidemiology of kidney replacement therapy between Europe and the United States: 2021 data of the ERA Registry and the USRDS.

BACKGROUND AND HYPOTHESIS: This paper compares the most recent data on the incidence and prevalence of kidney replacement therapy (KRT), kidney transplantation rates, and mortality on KRT from Europe to those from the United States (US), including comparisons of treatment modalities (haemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KTx)). METHODS: Data were derived from the annual reports of the European Renal Association (ERA) Registry and the United States Renal Data System (USRDS). The European data include information from national and regional renal registries providing the ERA Registry with individual patient data. Additional analyses were performed to present results for all participating European countries together. RESULTS: In 2021, the KRT incidence in the US (409.7 per million population (pmp)) was almost 3-fold higher than in Europe (144.4 pmp). Despite the substantial difference in KRT incidence, approximately the same proportion of patients initiated HD (Europe: 82%, US: 84%), PD (14%; 13% respectively), or underwent pre-emptive KTx (4%; 3% respectively). The KRT prevalence in the US (2436.1 pmp) was 2-fold higher than in Europe (1187.8 pmp). Within Europe, approximately half of all prevalent patients were living with a functioning graft (47%), while in the US, this was one third (32%). The number of kidney transplantations performed was almost twice as high in the US (77.0 pmp) compared to Europe (41.6 pmp). The mortality of patients receiving KRT was 1.6-fold higher in the US (157.3 per 1000 patient years) compared to Europe (98.7 per 1000 patient years). CONCLUSIONS: The US had a much higher KRT incidence, prevalence, and mortality compared to Europe, and despite a higher kidney transplantation rate, a lower proportion of prevalent patients with a functioning graft.

COVID-19 Pandemic in Dialysis Patients: The Swiss Experience.

Background: Chronic dialysis patients are classified as patients with increased risk for COVID-19. Knowledge about the incidence and survival of chronic dialysis patients infected with SARS-CoV-2 in Switzerland - a high-income country with high density of relatively small dialysis centers - is scarce. We present the findings regarding incidence, survival and regional differences, compared to those of the general population in Switzerland. Methods: Information on chronic dialysis patients who tested positive for SARS-CoV-2 between February 24, 2020 and February 28, 2022 were reported to the Swiss dialysis registry by all 94 Swiss dialysis centers. Hereafter, these results were linked with clinical characteristics from the Swiss dialysis registry. Results: Throughout the study period 1,120 out of ~4,700 dialysis patients tested positive for SARS-CoV-2 in Switzerland: 96 cases occurred in the first wave, 472 in the second wave and 5 in between. During the first wave, Italian-speaking Ticino was most severely affected, with a 7-fold higher incidence of dialysis patients compared to the general Swiss population. In the second wave, the majority of cases were found in the French-speaking part of Switzerland, with a 2.5 times higher incidence vs. non-dialysis patients. A total of 123 deaths were recorded in the first two waves, of which COVID-19 was the main cause of death in 100 patients. This corresponds to a highly increased overall mortality rate of 17.5% compared to 1.7% in the general population. Age was identified as the only risk factor for mortality in dialysis patients. During the third, fourth and fifth wave, 61, 43 and 443 cases, respectively, were recorded, resulting in 6 (mortality rate 9.8%), 1 (mortality rate 2.3%) and 13 deaths (mortality rate 2.9%). Conclusion: Chronic dialysis patients in Switzerland were more likely to be infected by SARS-CoV-2 during the first and second wave than the rest of the population, but an inverse trend was observed during the third, fourth and fifth wave, probably thanks to vaccination. In addition, mortality is significantly increased compared to non-dialysis patients. In Swiss dialysis patients, age is the strongest risk factor for death.

[Managing diabetic kidney disease]. / Diabetische Nephropathie.

Managing diabetic kidney disease Abstract. Diabetic kidney disease is a common complication of diabetes associated with an increased cardiovascular mortality and is the leading cause of end-stage renal disease. A heterogeneous set of pathological mechanisms drives the development and progression of diabetic kidney disease. A comprehensive diagnostic work-up and repeated reevaluation are needed since diabetic patients can suffer from other nephropathies with a clinical presentation similar to diabetic kidney disease. Screening, treatment of cardiovascular risk factors and the reduction of albuminuria, using renin-angiotensin-aldosterone system and sodium-dependent glucose transporter 2 inhibitors are crucial in the management of diabetic kidney disease.

Data from the ERA-EDTA Registry were examined for trends in excess mortality in European adults on kidney replacement therapy.

The objective of this study was to investigate whether the improvement in survival seen in patients on kidney replacement therapy reflects the enhanced survival of the general population. Patient and general population statistics were obtained from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry and the World Health Organization databases, respectively. Relative survival models were composed to examine trends over time in all-cause and cause-specific excess mortality, stratified by age and modality of kidney replacement therapy, and adjusted for sex, primary kidney disease and country. In total, 280,075 adult patients started kidney replacement therapy between 2002 and 2015. The excess mortality risk in these patients decreased by 16% per five years (relative excess mortality risk (RER) 0.84; 95% confidence interval 0.83-0.84). This reflected a 14% risk reduction in dialysis patients (RER 0.86; 0.85-0.86), and a 16% increase in kidney transplant recipients (RER 1.16; 1.07-1.26). Patients on dialysis showed a decrease in excess mortality risk of 28% per five years for atheromatous cardiovascular disease as the cause of death (RER 0.72; 0.70-0.74), 10% for non-atheromatous cardiovascular disease (RER 0.90; 0.88-0.92) and 10% for infections (RER 0.90; 0.87-0.92). Kidney transplant recipients showed stable excess mortality risks for most causes of death, although it did worsen in some subgroups. Thus, the increase in survival in patients on kidney replacement therapy is not only due to enhanced survival in the general population, but also due to improved survival in the patient population, primarily in dialysis patients.

Polypharmacy and Kidney Function in Community-Dwelling Adults Age 60 Years and Older: A Prospective Observational Study.

OBJECTIVES: Information on the impact of polypharmacy on kidney function in older adults is limited. We prospectively investigated the association between intake of total number of drugs or nonsteroidal anti-inflammatory drugs (NSAIDs) and kidney function. DESIGN: Our study is a prospective observational analysis of the 2-year Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis Patients. SETTING AND PARTICIPANTS: Of the 273 participants of the original trial, 270 participants (mean age 70.3 ± 6.4 years, 53% women) were included in this observational analysis. METHODS: The associations between (1) total number of drugs (or NSAIDs) at baseline or (2) cumulative number of drugs (or NASAIDs) repeatedly measured over 24 months and kidney function repeatedly measured over 24 months as estimated glomerular filtration rate (eGFR) were investigated using multivariable-adjusted repeated-measures analysis. RESULTS: Per drug at baseline, kidney function decreased by 0.64 mL/min/1.73 m2 eGFR (Beta = -0.64; 95% CI -1.19 to -0.08; P = .024) over 24 months. With every additional drug taken cumulatively over 24 months, kidney function decreased by 0.39 mL/min/1.73 m2 eGFR (Beta = -0.39; 95% CI -0.63 to -0.15; P = .002). In a high-risk subgroup, per NSAID taken cumulatively over 24 months, kidney function declined by 1.21 mL/min/1.73 m2 eGFR (Beta = -1.21; 95% CI -2.35 to -0.07; P = .021). CONCLUSIONS AND IMPLICATIONS: For every additional drug prescribed among older adults, our study supports an independent and immediate harmful impact on kidney function. This negative impact seems to be about 3 times greater for NSAIDs compared with an additional average drug.

The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2015: a summary.

BACKGROUND: This article summarizes the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry's 2015 Annual Report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2015 within 36 countries. METHODS: In 2016 and 2017, the ERA-EDTA Registry received data on patients who were undergoing RRT for ESRD in 2015, from 52 national or regional renal registries. Thirty-two registries provided individual patient-level data and 20 provided aggregated-level data. The incidence, prevalence and survival probabilities of these patients were determined. RESULTS: In 2015, 81 373 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 119 per million population (pmp). The incidence ranged by 10-fold, from 24 pmp in Ukraine to 232 pmp in the Czech Republic. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 85% of the patients, peritoneal dialysis for 11% and a kidney transplant for 4%. By Day 91 of commencing RRT, 82% of patients were receiving haemodialysis, 13% peritoneal dialysis and 5% had a kidney transplant. On 31 December 2015, 546 783 individuals were receiving RRT for ESRD, corresponding to an unadjusted prevalence of 801 pmp. This ranged throughout Europe by more than 10-fold, from 178 pmp in Ukraine to 1824 pmp in Portugal. In 2015, 21 056 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 31 pmp. This varied from 2 pmp in Ukraine to 94 pmp in the Spanish region of Cantabria. For patients commencing RRT during 2006-10, the 5-year unadjusted patient survival probabilities on all RRT modalities combined was 50.0% (95% confidence interval 49.9-50.1).

The European Renal Association - European Dialysis and Transplant Association Registry Annual Report 2014: a summary.

Background: This article summarizes the European Renal Association - European Dialysis and Transplant Association Registry's 2014 annual report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2014 within 35 countries. Methods: In 2016, the ERA-EDTA Registry received data on patients who in 2014 where undergoing RRT for ESRD, from 51 national or regional renal registries. Thirty-two registries provided individual patient level data and 19 provided aggregated patient level data. The incidence, prevalence and survival probabilities of these patients were determined. Results: In 2014, 70 953 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 133 per million population (pmp). The incidence ranged by 10-fold; from 23 pmp in the Ukraine to 237 pmp in Portugal. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. By day 91 of commencing RRT, 81% of patients were receiving haemodialysis. On 31 December 2014, 490 743 individuals were receiving RRT for ESRD, equating to an unadjusted prevalence of 924 pmp. This ranged throughout Europe by more than 10-fold, from 157 pmp in the Ukraine to 1794 pmp in Portugal. In 2014, 19 406 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 36 pmp. Again this varied considerably throughout Europe. For patients commencing RRT during 2005-09, the 5-year-adjusted patient survival probabilities on all RRT modalities was 63.3% (95% confidence interval 63.0-63.6). The expected remaining lifetime of a 20- to 24-year-old patient with ESRD receiving dialysis or living with a kidney transplant was 21.9 and 44.0 years, respectively. This was substantially lower than the 61.8 years of expected remaining lifetime of a 20-year-old patient without ESRD.

Therapeutic Efficacy and Cost Effectiveness of High Cut-Off Dialyzers Compared to Conventional Dialysis in Patients with Cast Nephropathy.

BACKGROUND: High Cut-Off (HCO) dialysis membranes efficiently reduce serum free light chain (FLC) concentrations and may improve renal recovery and survival from multiple myeloma (MM) associated renal failure with cast nephropathy. However, clinical trials comparing dialysis with HCO versus conventional filters are lacking. The aim of this study was to assess clinical outcomes and economic impact of HCO dialyzers compared to conventional hemodialysis membranes in cast nephropathy. METHODS: Multicenter retrospective analysis of 19 patients treated for renal failure from FLC associated cast nephropathy with standard induction chemotherapy (bortezomib/dexamethasone). We compared hemodialysis treatment with High Cut-Off (n = 12) versus conventional dialyzers (n = 7). Primary endpoint was survival; secondary endpoints were renal recovery, renal function and treatment costs. RESULTS: At 12 months, patient survival was 25% in the HCO group versus 0% in controls (p = NS). A tendency towards faster renal recovery (p = 0.066) and better renal function at 3, 6 and 12 months (p = 0.109) after diagnosis of MM was noted in the HCO group. Complete renal response rate was achieved in 10.5 and 0% of HCO and control patients, respectively, partial renal response in 15.8 and 5.3%, and minor renal response in 26.3 and 15.8%, respectively. Both patient survival and renal recovery were significantly correlated with the extent of free light chain (FLC) reduction in serum. Median treatment costs were CHF 230'000 and 223'000 (p = NS) in the HCO and control group, respectively. CONCLUSIONS: Hemodialysis treatment with HCO membranes for cast nephropathy tended towards better survival as well as faster and better recovery of renal function versus conventional dialyzers. Moreover, total medical costs were comparable between groups. In the absence of results from randomized prospective trials on this topic, the use of HCO dialyzers in patients with renal failure from cast nephropathy may be recommended. Prospective randomized trials are required.

Quantification of excretory renal function and urinary protein excretion by determination of body cell mass using bioimpedance analysis.

BACKGROUND: Creatinine clearance (CrCl) based on 24 h urine collection is an established method to determine glomerular filtration rate (GFR). However, its measurement is cumbersome and the results are frequently inaccurate. The aim of this study was to develop an alternative method to predict CrCl and urinary protein excretion based on plasma creatinine and the quantification of muscle mass through bioimpedance analysis (BIA). METHODS: In 91 individuals with normal and impaired renal function CrCl was measured from 24 h urine excretion and plasma creatinine concentration. A model to predict 24 h-creatininuria was developed from various measurements assessing muscle mass such as body cell mass (BCM) and fat free mass (FFM) obtained by BIA, skinfold caliper and other techniques (training group, N = 60). Multivariate regression analysis was performed to predict 24 h-creatininuria and to calculate CrCl. A validation group (N = 31) served to compare predicted and measured CrCl. RESULTS: Overall (accuracy, bias, precision, correlation) the new BIA based prediction model performed substantially better compared with measured CrCl (P15 = 87 %, bias = 0, IQR of differences = 7.9 mL/min/1.73 m(2), R = 0.972) versus established estimation formulas such as the 4vMDRD (P15 = 6 %, bias = -8.3 mL/min/1.73 m(2), IQR = 13.7 mL/min/1.73 m(2), R = 0.935), CKD-EPI (P15 = 29 %, bias = -7.0 mL/min/1.73 m(2), IQR = 12.1 mL/min/1.73 m(2), R = 0.932, Cockcroft-Gault equations (P15 = 55 %, bias = -4.4 mL/min/1.73 m(2), IQR = 9.0 mL/min/1.73 m(2), R = 0.920). The superiority of the new method over established prediction formulas was most obvious in a subgroup of individuals with BMI > 30 kg/m(2) and in a subgroup with CrCl > 60 mL/min/1.73 m(2). Moreover, 24 h urinary protein excretion could be estimated accurately by normalization with 24 h-creatininuria derived from BIA based BCM. CONCLUSION: Prediction of CrCl based on estimated urinary creatinine excretion determined from measurement of BCM by BIA technique is both accurate and convenient to quantify renal function in normal and diseased states. This new method may become particularly helpful for the evaluation of patients with borderline renal insufficiency and/or with abnormal body composition.

A randomized, open-label trial of iron isomaltoside 1000 (Monofer®) compared with iron sucrose (Venofer®) as maintenance therapy in haemodialysis patients.

BACKGROUND: Iron deficiency anaemia is common in patients with chronic kidney disease, and intravenous iron is the preferred treatment for those on haemodialysis. The aim of this trial was to compare the efficacy and safety of iron isomaltoside 1000 (Monofer®) with iron sucrose (Venofer®) in haemodialysis patients. METHODS: This was an open-label, randomized, multicentre, non-inferiority trial conducted in 351 haemodialysis subjects randomized 2:1 to either iron isomaltoside 1000 (Group A) or iron sucrose (Group B). Subjects in Group A were equally divided into A1 (500 mg single bolus injection) and A2 (500 mg split dose). Group B were also treated with 500 mg split dose. The primary end point was the proportion of subjects with haemoglobin (Hb) in the target range 9.5-12.5 g/dL at 6 weeks. Secondary outcome measures included haematology parameters and safety parameters. RESULTS: A total of 351 subjects were enrolled. Both treatments showed similar efficacy with >82% of subjects with Hb in the target range (non-inferiority, P = 0.01). Similar results were found when comparing subgroups A1 and A2 with Group B. No statistical significant change in Hb concentration was found between any of the groups. There was a significant increase in ferritin from baseline to Weeks 1, 2 and 4 in Group A compared with Group B (Weeks 1 and 2: P < 0.001; Week 4: P = 0.002). There was a significant higher increase in reticulocyte count in Group A compared with Group B at Week 1 (P < 0.001). The frequency, type and severity of adverse events were similar. CONCLUSIONS: Iron isomaltoside 1000 and iron sucrose have comparative efficacy in maintaining Hb concentrations in haemodialysis subjects and both preparations were well tolerated with a similar short-term safety profile.

The prevalence of chronic kidney disease in a primary care setting: a Swiss cross-sectional study.

Chronic kidney disease (CKD) often remains clinically silent and therefore undiagnosed until a progressed stage is reached. Our aim was to estimate the prevalence of CKD in a primary care setting in Switzerland. A multicenter, cross-sectional study with randomly selected general practitioners was performed. Adults visiting their general physician's cabinet during defined periods were asked to participate. Baseline information was reported on a questionnaire, urine and blood samples were analyzed in a central laboratory. Renal status was assessed using the Kidney Disease: Improving Global Outcomes (KDIGO) classification. Extrapolation of results to national level was adjusted for age and gender. One thousand individuals (57% females) with a mean age of 57 ± 17 years were included. Overall, 41% of the patients had normal estimated glomerular filtration rate (eGFR) and albumin creatinine ratio (ACR), whereas 36% of the subjects had slightly reduced excretory renal function with physiological albuminuria based on normal ACR. Almost one fourth of the subjects (23%) had either a substantially reduced eGFR or high levels of ACR. About 10% of the patients had a substantially reduced eGFR of <60 ml/min/1.73 m(2), and 17% showed relevant proteinuria (ACR >30 mg/g creatinine). Extrapolation to national level suggests that about 18% of primary care patients may suffer from CKD. CKD prevalence in a primary care population is therefore high, and preventive interventions may be advisable, in particular as CKD prevalence is likely to rise over the next decades.

Epidemiologic trends in chronic renal replacement therapy over forty years: a Swiss dialysis experience.

BACKGROUND: Long term longitudinal data are scarce on epidemiological characteristics and patient outcomes in patients on maintenance dialysis, especially in Switzerland. We examined changes in epidemiology of patients undergoing renal replacement therapy by either hemodialysis or peritoneal dialysis over four decades. METHODS: Single center retrospective study including all patients which initiated dialysis treatment for ESRD between 1970 and 2008. Analyses were performed for subgroups according to dialysis vintage, based on stratification into quartiles of date of first treatment. A multivariate model predicting death and survival time, using time-dependent Cox regression, was developed. RESULTS: 964 patients were investigated. Incident mean age progressively increased from 48 ± 14 to 64 ± 15 years from 1st to 4th quartile (p < 0.001), with a concomitant decrease in 3- and 5-year survival from 72.2 to 67.7%, and 64.1 to 54.8%, respectively. Nevertheless, live span continuously increased from 57 ± 13 to 74 ± 11 years (p < 0.001). Patients transplanted at least once were significantly younger at dialysis initiation, with significantly better survival, however, shortened live span vs. individuals remaining on dialysis. Among age at time of initiating dialysis therapy, sex, dialysis modality and transplant status, only transplant status is a significant independent covariate predicting death (HR: 0.10 for transplanted vs. non-transplanted patients, p = 0.001). Dialysis vintage was associated with better survival during the second vs. the first quartile (p = 0.026). DISCUSSION: We document an increase of a predominantly elderly incident and prevalent dialysis population, with progressively shortened survival after initiation of renal replacement over four decades, and, nevertheless, a prolonged lifespan. Analysis of the data is limited by lack of information on comorbidity in the study population. CONCLUSIONS: Survival in patients on renal replacement therapy seems to be affected not only by medical and technical advances in dialysis therapy, but may mostly reflect progressively lower mortality of individuals with cardiovascular and metabolic complications, as well as a policy of accepting older and polymorbid patients for dialysis in more recent times. This is relevant to make demographic predictions in face of the ESRD epidemic nephrologists and policy makers are facing in industrialized countries.

Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality.

BACKGROUND: Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. METHODS: This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. RESULTS: Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. CONCLUSIONS: Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

Protein intake in renal and hepatic disease.

The kidney and the liver play a central role in protein metabolism. Synthesis of albumin and other proteins occurs mainly in the liver, whereas protein breakdown and excretion are handled through an intricate interaction between these two organ systems. Thus, disease states of either the liver and/or the kidney invariably result in clinically relevant disturbances of protein metabolism. Conversely, metabolic processes regulated by these two organs are directly affected by dietary protein intake. Of particular importance in this respect is the maintenance of acid/base homeostasis. Finally, both the amount and composition of ingested proteins have a direct impact on renal function, especially in a state of diseased kidneys. Consequently, dietary protein intake is of paramount importance in patients with chronic nephropathy and renal insufficiency. Limitation of ingested protein, particularly from animal sources, is crucial in order to slow the progression of chronic kidney disease and impaired renal function. In contrast, patients with chronic renal failure undergoing renal replacement therapy by hemodialysis or peritoneal dialysis, have an increased protein demand. The syndrome of "protein-energy malnutrition" is a relevant factor for morbidity and mortality in this population and requires early detection and vigorous treatment. Protein intake in patients with cirrhosis of the liver should not be diminished as has been earlier suggested but rather increased to 1.0 - 1.2 g/kg body weight/day, in order to prevent protein malnutrition. Moderate restriction depending on protein tolerance (0.5 - 1.2 g/kg body weight/day), with the possible addition of branched chain amino acids (BCAA), has been recommended only in patients with advanced hepatic encephalopathy. Proteins of plant origin are theoretically superior to animal proteins.

Basal cell carcinoma in a series of renal transplant recipients: epidemiology and clinicopathologic features.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy among Caucasians worldwide. The risk of BCC is 10-16 times higher among immunosuppressed transplant recipients compared with the general population. OBJECTIVE: To analyze the incidence, clinical presentation, histologic features, treatment and recurrence rate of BCC in a cohort of 69 renal transplant recipients (RTRs; 53 male). METHODS: Retrospective population-based cohort study of immunosuppressed RTRs. RESULTS: Ten of 69 patients (14.5%, five male) developed a total of 17 BCCs, mostly on the head. Mean age at first diagnosis of BCC was 65.5 +/- 8.5 years, and latency between kidney transplantation and diagnosis of the first BCC was 11.1 +/- 6.3 years (mean +/- SD). The risk of female RTRs to develop BCCs appeared to be three times higher than the risk of male RTRs, and female RTRs developed BCCs earlier after transplantation. Nodular BCC was the most common histologic subtype. Most BCCs in these RTRs were treated by complete surgical excision. Recurrence after surgical excision was observed in one of the 10 patients (10%). CONCLUSION: Our results suggest female RTRs to be at higher risk to develop cutaneous BCCs than male RTRs. There are no differences in localization and clinicopathologic presentation of BCCs developing in RTRs compared with immunocompetent patients. Therefore, BCCs in RTRs do not require different treatment than in other patient groups. As patients tend to develop a second BCC, close follow-up is mandatory.

Pregnancy-associated plasma protein-A is an independent short-time predictor of mortality in patients on maintenance haemodialysis.

AIMS: Mortality of maintenance haemodialysis (HD) patients is very high due to polymorbidity, mostly from metabolic and cardiovascular disease. In order to identify patients with high risk for life-threatening complications, reliable prognostic markers would be helpful. Pregnancy-associated plasma protein-A (PAPP-A) has been shown to predict cardiovascular events and death in patients with stable coronary artery disease as well as in acute coronary syndrome in patients with normal renal function. It was the aim of this study to evaluate PAPP-A as a marker for death in patients on maintenance HD. METHODS AND RESULTS: PAPP-A serum levels were measured in 170 patients participating in the monitor! trial, a prospective dynamic dialysis cohort multicenter study in Switzerland. Patients were followed up for a median time of 17 months after measuring PAPP-A, and evaluated for death of any cause. Survivors and non-survivors were compared with regard to baseline PAPP-A concentrations. A multivariate logistic regression analysis for death was performed including PAPP-A, age, sex, number of comorbidities, dialysis vintage, Kt/V, IL-6, C-reactive protein, parathyroid hormone (PTH), Ca x PO(4) product, and total serum cholesterol. A cut-off value for PAPP-A was calculated for discrimination between patients with low and high mortality risk, respectively. A total of 23 deaths occurred during follow-up, equalling an incidence rate of 0.1. Baseline median PAPP-A levels were 40% higher in non-survivors vs. survivors (P = 0.023). In a multivariate analysis, only PAPP-A, age, and Ca x PO(4) product were independent predictors of mortality. A cut-off value of 24 mIU/L discriminates significantly (P = 0.015) between patients at low or high risk for death with a negative predictive value of 91%. CONCLUSION: PAPP-A is a novel and independent short-time predictor of mortality in a maintenance HD population. The pathogenetic relevance of PAPP-A, particularly in the development of cardiovascular disease, remains to be further elucidated.

Impact of gastrointestinal-related side effects on mycophenolate mofetil dosing and potential therapeutic strategies.

In renal transplant patients receiving mycophenolate mofetil (MMF), maintaining an adequate dosing regimen has been shown to maximize short- and long-term outcomes. Gastrointestinal (GI) adverse events associated with MMF are frequent, and lead to MMF dose reduction or withdrawal in 40-50% of cases. Among MMF-treated patients experiencing GI complications, one analysis has reported MMF discontinuation to be associated with almost a threefold increase in risk of graft loss, while a dose reduction > or = 50% carried over a twofold increase in risk. If GI symptoms improve and the pre-reduction MMF dose is resumed the increased risk of graft loss may be reversed, but continuing intolerance can make this difficult to achieve. Investigation of contributing factors is important and may alleviate symptoms. Conversion to enteric-coated mycophenolate sodium (EC-MPS) may be an effective option. Two open-label studies using patient-reported outcomes data have shown a significant and clinically relevant benefit in GI-related symptom burden after conversion from MMF to EC-MPS. In conclusion, monitoring of GI complications is essential following renal transplantation, and maintaining adequate mycophenolic acid exposure should be a priority when considering treatment options.