Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge.

Peritoneal dialysis (PD) is a home-based efficacious modality for the replacement of renal function in end-stage kidney failure patients, but it is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of the long-term morpho-functional peritoneal changes that eventually result in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile is proving to be quite difficult. New approaches targeting the composition of the PD solution include the replacement of glucose with other osmotic agents, and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include the infusion of mesenchymal cells or the administration of orally active agents. In the present article, we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

Biomarker-Development Proteomics in Kidney Transplantation: An Updated Review.

Kidney transplantation (KT) is the optimal therapeutic strategy for patients with end-stage renal disease. The key to post-transplantation management is careful surveillance of allograft function. Kidney injury may occur from several different causes that require different patient management approaches. However, routine clinical monitoring has several limitations and detects alterations only at a later stage of graft damage. Accurate new noninvasive biomarker molecules are clearly needed for continuous monitoring after KT in the hope that early diagnosis of allograft dysfunction will lead to an improvement in the clinical outcome. The advent of "omics sciences", and in particular of proteomic technologies, has revolutionized medical research. Proteomic technologies allow us to achieve the identification, quantification, and functional characterization of proteins/peptides in biological samples such as urine or blood through supervised or targeted analysis. Many studies have investigated proteomic techniques as potential molecular markers discriminating among or predicting allograft outcomes. Proteomic studies in KT have explored the whole transplant process: donor, organ procurement, preservation, and posttransplant surgery. The current article reviews the most recent findings on proteomic studies in the setting of renal transplantation in order to better understand the effective potential of this new diagnostic approach.

Predialysis and Dialysis Therapies Differently Affect Nitric Oxide Synthetic Pathway in Red Blood Cells from Uremic Patients: Focus on Peritoneal Dialysis.

Red blood cells (RBCs) have been found to synthesize and release both nitric oxide (NO) and cyclic guanosine monophosphate (cGMP), contributing to systemic NO bioavailability. These RBC functions resulted impaired in chronic kidney disease (CKD). This study aimed to evaluate whether predialysis (conservative therapy, CT) and dialysis (peritoneal dialysis, PD; hemodialysis, HD) therapies used during CKD progression may differently affect NO-synthetic pathway in RBCs. Our data demonstrated that compared to PD, although endothelial-NO-synthase activation was similarly increased, HD and CT were associated to cGMP RBCs accumulation, caused by reduced activity of cGMP membrane transporter (MRP4). In parallel, plasma cGMP levels were increased by both CT and HD and they significantly decreased after hemodialysis, suggesting that this might be caused by reduced cGMP renal clearance. As conceivable, compared to healthy subjects, plasma nitrite levels were significantly reduced by HD and CT but not in patients on PD. Additionally, the increased carotid intima-media thickness (IMT) values did not reach the significance exclusively in patients on PD. Therefore, our results show that PD might better preserve the synthetic NO-pathway in CKD-erythrocytes. Whether this translates into a reduced development of uremic vascular complications requires further investigation.

Nephrotoxicity Associated with Novel Anticancer Agents (Aflibercept, Dasatinib, Nivolumab): Case Series and Nephrological Considerations.

Cancer patients have an incidence of about 60% kidney disease development and are at elevated risk of acute renal damage. Kidney disease in these patients is frequently associated with nephrotoxicity from the ongoing oncological treatment. New anticancer therapeutic strategies, such as targeted therapies and immunotherapies, offer substantial benefits in the treatment of many neoplasms. However, their use is associated with significant nephrotoxicity, which qualitatively differs from that seen with traditional cytotoxic chemotherapy, while the underlying mechanisms are complex and still to be clearly defined. Nephrologists need to be knowledgeable about the array of such renal toxicities for effective collaboration with the oncologist in the prevention and management of kidney involvement. Renal adverse effects may range from asymptomatic proteinuria to renal failure, and their prompt identification and timely treatment is essential for optimal and safe care of the patient. In this article, after presenting clinical cases we discuss the differing renal toxicity of three novel anticancer agents (aflibercept, dasatinib, and nivolumab) and possible measures to counter it.

Recovery Time after Hemodialysis Is Inversely Associated with the Ultrafiltration Rate.

INTRODUCTION: The present study aimed to determine the variables that are associated with a longer dialysis recovery time (DRT) and to define the relationship that exists between DRT and the ultrafiltration rate (UFR) in prevalent chronic hemodialysis (CHD) patients. METHODS: We studied 210 prevalent CHD of 5 hemodialysis units in Central Italy. Patients were invited to answer to the question: "How long does it take you to recover from a dialysis session?" Answers to this question were subsequently converted into minutes. Demographic, clinical and laboratory parameters were recorded for each patient as well as the UFR (mL/kg/h), the dialysate sodium concentration and temperature. RESULTS: Median DRT was 180 min (60-420). Ninety five (45%) patients had a DRT ≥ the median value. Mean UFR was 9.2 ± 3.0 mL/kg/h. Patients with a lower DRT had a less prevalent disability in the instrumental activities daily living, had a higher UFR, and a lower dialysate temperature, as compared with subjects with higher DRT. According to the logistic regression model, UFR was associated with a DRT below the median (i.e., 180) in the unadjusted model (OR 1.12; 95% CI 1.02-1.23; p = 0.019), after adjusting for age and sex (OR 1.11; 95% CI 1.01-1.22; p = 0.025), and in the fully adjusted model (OR 1.11; 95% CI 1.04-1.22; p = 0.040). UFR increase was associated with increasing probability of DRT below the median (p for trend = 0.035). The highest tertile of DRT was associated with UFR below the mean value (i.e., 9.2 mL/kg/h) in multinomial logistic regression having the lowest DRT tertile as reference. DRT was significantly lower in patients with UFR > 13 mL/kg/h than in patients with UFR 10-13 or < 10 mL/kg/h. CONCLUSION: DRT is inversely associated with UFR in CHD patients. Whether a high UFR should be recommended to reduce the DRT needs to be elucidated through an adequate prospective randomized study.

Urinary Peptidomic Biomarkers in Kidney Diseases.

In order to effectively develop personalized medicine for kidney diseases we urgently need to develop highly accurate biomarkers for use in the clinic, since current biomarkers of kidney damage (changes in serum creatinine and/or urine albumin excretion) apply to a later stage of disease, lack accuracy, and are not connected with molecular pathophysiology. Analysis of urine peptide content (urinary peptidomics) has emerged as one of the most attractive areas in disease biomarker discovery. Urinary peptidome analysis allows the detection of short and long-term physiological or pathological changes occurring within the kidney. Urinary peptidomics has been applied extensively for several years now in renal patients, and may greatly improve kidney disease management by supporting earlier and more accurate detection, prognostic assessment, and prediction of response to treatment. It also promises better understanding of kidney disease pathophysiology, and has been proposed as a "liquid biopsy" to discriminate various types of renal disorders. Furthermore, proteins being the major drug targets, peptidome analysis may allow one to evaluate the effects of therapies at the protein signaling pathway level. We here review the most recent findings on urinary peptidomics in the setting of the most common kidney diseases.

Prevalence and associated variables of post-dialysis fatigue: Results of a prospective multicentre study.

AIM: The study aims to determine prevalence and severity of PDF and to define its associated variables. METHODS: In five haemodialysis units of northern-centre Italy, patients were regarded to suffer from PDF if they spontaneously offered this complaint when asked the open-ended question: Do you feel better or worse after dialysis? If worse, please specify in which way. A complaint of fatigue would be probed further with questions directed at its duration, frequency and intensity, allowing creation of a fatigue index of severity (one third of the sum of these three parameters, each rated from 1 to 5). Patients were stratified into three groups according the severity of PDF: 1) score = 0; 2) score = 1-3; 3) score > 3. RESULTS: We studied 271 patients: 164 had PDF and 107 did not. PDF patients had significantly longer time of recovery after dialysis (TIRD). TIRD was significantly associated with PDF duration, intensity, and frequency. Patients with PDF were older and had a lower ADL score. At multivariate analysis, PDF was significantly associated with TIRD. In a multivariate model that did not include TIRD, PDF was independently associated with age and ADL. Sixty patients had moderate PDF and 104 had severe PDF. In patients with severe PDF, age and dialytic age were higher, ADL and IADL scores were lower, TIRD was longer and the ultrafiltration rate was lower. At multivariate analysis, PDF severity was independently associated with TIRD. In the model without TIRD, PDF severity was associated with ADL only. CONCLUSION: Post-dialysis fatigue is frequent and associated with age and ADL. Dialytic variables seem unrelated to PDF.

New Treatment Approaches for the Anemia of CKD.

Normocytic normochromic anemia is a common complication in chronic kidney disease and is associated with many adverse clinical consequences. Erythropoiesis-stimulating agents (ESAs) and adjuvant iron therapy represent the primary treatment for anemia in chronic kidney disease. The introduction of ESAs into clinical practice was a success story, mediating an increase in hemoglobin concentrations without the risk for recurrent blood transfusions and improving quality of life substantially. However, recombinant ESAs are still expensive and require a parenteral route of administration. Moreover, concern has arisen following randomized clinical trials showing that higher hemoglobin targets and/or high ESA doses may cause significant harm. This, together with changes in ESA reimbursement policy in some countries, has resulted in a significant reduction in ESA prescribing and the hemoglobin level targeted during therapy. Several attempts are being made to develop new drugs with improved characteristics and/or easier manufacturing processes compared with currently available ESAs, including new treatment approaches that may indirectly improve erythropoiesis. We give an update on the new investigational strategies for increasing erythropoiesis, examining in depth their characteristics and possible advantages in the clinical setting and the caveats to be aware of at the present stage of development.

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients.

Red blood cells (RBCs) enzymatically produce nitric oxide (NO) by a functional RBC-nitric oxide synthase (RBC-NOS). NO is a vascular key regulatory molecule. In RBCs its generation is complex and influenced by several factors, including insulin, acetylcholine, and calcium. NO availability is reduced in end-stage renal disease (ESRD) and associated with endothelial dysfunction. We previously demonstrated that, through increased phosphatidylserine membrane exposure, ESRD-RBCs augmented their adhesion to human cultured endothelium, in which NO bioavailability decreased. Since RBC-NOS-dependent NO production in ESRD is unknown, this study aimed to investigate RBC-NOS levels/activation, NO production/bioavailability in RBCs from healthy control subjects (C, N = 18) and ESRD patients (N = 27). Although RBC-NOS expression was lower in ESRD-RBCs, NO, cyclic guanosine monophosphate (cGMP), RBC-NOS Serine1177 phosphorylation level and eNOS/Calmodulin (CaM)/Heat Shock Protein-90 (HSP90) interaction levels were higher in ESRD-RBCs, indicating increased enzyme activation. Conversely, following RBCs stimulation with insulin or ionomycin, NO and cGMP levels were significantly lower in ESRD- than in C-RBCs, suggesting that uremia might reduce the RBC-NOS response to further stimuli. Additionally, the activity of multidrug-resistance-associated protein-4 (MRP4; cGMP-membrane transporter) was significantly lower in ESRD-RBCs, suggesting a possible compromised efflux of cGMP across the ESRD-RBCs membrane. This study for the first time showed highest basal RBC-NOS activation in ESRD-RBCs, possibly to reduce the negative impact of decreased NOS expression. It is further conceivable that high NO production only partially affects cell function of ESRD-RBCs maybe because in vivo they are unable to respond to physiologic stimuli, such as calcium and/or insulin.

Proteomic Investigations into Hemodialysis Therapy.

The retention of a number of solutes that may cause adverse biochemical/biological effects, called uremic toxins, characterizes uremic syndrome. Uremia therapy is based on renal replacement therapy, hemodialysis being the most commonly used modality. The membrane contained in the hemodialyzer represents the ultimate determinant of the success and quality of hemodialysis therapy. Membrane's performance can be evaluated in terms of removal efficiency for unwanted solutes and excess fluid, and minimization of negative interactions between the membrane material and blood components that define the membrane's bio(in)compatibility. Given the high concentration of plasma proteins and the complexity of structural functional relationships of this class of molecules, the performance of a membrane is highly influenced by its interaction with the plasma protein repertoire. Proteomic investigations have been increasingly applied to describe the protein uremic milieu, to compare the blood purification efficiency of different dialyzer membranes or different extracorporeal techniques, and to evaluate the adsorption of plasma proteins onto hemodialysis membranes. In this article, we aim to highlight investigations in the hemodialysis setting making use of recent developments in proteomic technologies. Examples are presented of why proteomics may be helpful to nephrology and may possibly affect future directions in renal research.

Use of Proton Pump Inhibitors Is Not Associated with Post-Dialysis Fatigue and Time of Recovery after Dialysis in Patients on Maintenance Hemodialysis.

Objectives: To define if the use of proton pump inhibitors (PPI) is associated with PDF prevalence and characteristics and with time of recovery after dialysis in patients on maintenance hemodialysis. Methods: Patients were defined as experiencing PDF if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Time of recovery after dialysis (TIRD) was also assessed for each patient. Each patient was invited to rate the intensity, duration and frequency of PDF from 1 to 5. We defined if patients used PPI (no PPI use or PPI use), the type of used PPI, the dose of used PPI, and the duration of the use of PPI (<1 year or ≥1 year). Results: A total of 346 patients were studied: 259 used PPI (55 used omeprazole, 63 esomeprazole, 54 pantoprazole, 87 lansoprazole, and 7 rabeprazole) and 87 did not. Two hundred and thirty-two patients declared PDF and 114 did not. The median [min-max] TIRD was 210 min [0-1440]. The prevalence of PDF in PPI users and PPI non-users was 67% and 68%, respectively (p = 0.878). The median [min-max] TIRD did not differ significantly between PPI users and PPI non-users (180 [0-1440] and 240 [0-1440], respectively; p = 0.871). Median PDF intensity, duration, frequency, and severity did not differ significantly between PPI use and no use. The prevalence of PDF was similar among the different types of PPI use and did not differ with respect to PPI non-users. Duration of PPI exposure was <1 year in 40 patients and ≥1 year in 219 patients. The prevalence of PDF did not differ between the two exposures. The correlation matrix between PPI equivalent dose, PPI treatment duration and PDF frequency, PDF characteristics, and TIRD showed whether there was statistical significance. Conclusions: The use of PPI is not associated with PDF and time of recovery after dialysis in patients on maintenance hemodialysis.

Treatment Options for Anemia in Kidney Transplant Patients: A Review.

Anemia is common after kidney transplantation. The etiology may be multifactorial, such as causes of anemia in the general population and causes that are unique to the kidney transplant setting. Posttransplant anemia, particularly when severe, may be associated with adverse effects such as graft failure, mortality, and a decline in kidney function. After careful investigation, that is, having excluded or treated reversible causes of anemia, treatment of anemia in patients with a kidney transplant is based on iron supplementation or erythropoiesis-stimulating agents (ESA), although there are no specific guidelines on anemia management in this patient population. Iron therapy is often needed, but optimal and safe iron-deficiency management strategies remain to be defined. Evidence suggests that ESAs are safe and potentially associated with favorable outcomes. Better graft function has been reported with ESA use targeting hemoglobin levels higher than those recommended in the general population with chronic kidney disease and with no apparent increased risk of cardiovascular events. These results require further investigation. Data on the use of hypoxia-inducible factor inhibitors are limited. Prevention and treatment of anemia in kidney transplantation can improve patients' quality of life, life expectancy, allograft function, and survival.

Efficacy of hemoperfusion with Seraph-100 in series with single pass albumin dialysis in acute hepatitis B infection: A case report.

Acute and acute-on-chronic liver failure is a cause of death in patients suffering from viral hepatitis, and many cases need liver transplantation. Infection from hepatitis B virus may range from asymptomatic to severe acute and fulminant hepatitis. In this setting, treatment is mainly supportive as there is no consensus on antiviral therapy based on non-nucleoside reverse transcriptase inhibitors. Single-pass albumin dialysis is a liver-support technique for patients suffering from liver failure, that has shown effectiveness in the removal of both water-soluble and albumin-bound toxins, which accumulate due to impairment of the liver's cleansing function. We report here the case of a 62-year-old male who presented with a severe acute hepatitis B infection, liver failure, and marked hyperbilirubinemia. Treatment with single-pass albumin dialysis combined with a hemoperfusion device was successful in improving clinical, physiological, and laboratory parameters.

Chyloperitoneum in Peritoneal Dialysis Secondary to Calcium Channel Blocker Use: Case Series and Literature Review.

Chyloperitoneum (chylous ascites) is a rare complication of peritoneal dialysis (PD). Its causes may be traumatic and nontraumatic, associated with neoplastic disease, autoimmune disease, retroperitoneal fibrosis, or rarely calcium antagonist use. We describe six cases of chyloperitoneum occurring in patients on PD as a sequel to calcium channel blocker use. The dialysis modality was automated PD (two patients) and continuous ambulatory PD (the rest of the patients). The duration of PD ranged from a few days to 8 years. All patients had a cloudy peritoneal dialysate, characterized by a negative leukocyte count and sterile culture tests for common germs and fungi. Except for in one case, the cloudy peritoneal dialysate appeared shortly after the initiation of calcium channel blockers (manidipine, n = 2; lercanidipine, n = 4), and cleared up within 24-72 h after withdrawal of the drug. In one case in which treatment with manidipine was resumed, peritoneal dialysate clouding reappeared. Though turbidity of PD effluent is due in most cases to infectious peritonitis, there are other differential causes including chyloperitoneum. Although uncommon, chyloperitoneum in these patients may be secondary to the use of calcium channel blockers. Being aware of this association can lead to prompt resolution by suspension of the potentially offending drug, avoiding stressful situations for the patient such as hospitalization and invasive diagnostic procedures.

Post-dialysis fatigue: Comparison of bicarbonate hemodialysis and online hemodiafiltration.

INTRODUCTION: The present cross-sectional study aimed to compare the prevalence, the characteristics of post-dialysis fatigue and the length of recovery time after hemodialysis in prevalent end-stage renal disease patients (ESRD) receiving bicarbonate hemodialysis (HD) or hemodiafiltration (HDF). METHODS: Patients were suffering from post-dialysis fatigue if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Moreover, each patient was invited to rate the intensity, duration, and frequency of post-dialysis fatigue from 1 to 5. In order to assess RECOVERY TIME AFTER DIALYSIS, patients were invited to answer to the following single open-ended question: "How long does it take you to recover from a dialysis session?" FINDINGS: We included 335 patients: 252 received HD and 83 received HDF. Post-dialysis fatigue was present in 204 patients (60.9%). Prevalence of post-dialysis fatigue did not differ significantly between patients on HD (62.3%) and on HDF (56.6%; p = 0.430). Median recovery time after dialysis was 180 min [180-240] and did not differ significantly between the two subgroups (180 min [130-240] and 240 min [120-332] p = 0.671, respectively). Median post-dialysis fatigue intensity, duration, and frequency were 3 [1-5], 3 [1-5], and 4 [1-5] and did not differ significantly between patients on HD and on HDF. At the multivariate analysis, age, ADL and hemoglobin levels were the independent predictors of the HDF treatment. DISCUSSION: Prevalence and characteristics of post-dialysis fatigue do not differ significantly between patients receiving bicarbonate HD or HDF.

[Leukapheresis and chronic inflammatory bowel disease: an additional obligation for the nephrologist]. / La leucocitoaferesi nella patologia infiammatoria cronica intestinale: un ''impegno'' aggiuntivo per il nefrologo.

The current treatment of chronic inflammatory bowel diseases involves the administration of different immunosuppressive drugs, whose use is associated with several side effects. Among the treatment alternatives, clinicians are attracted by leukapheresis, a method able to selectively remove from the circulation molecules involved in the onset and maintenance of inflammation. From 2007 to 2008, six patients were recruited from our clinics; four patients were affected by ulcerative colitis and two by Crohn's disease. They presented symptoms including abdominal pain and diarrhea despite treatment with steroids and sulfasalazine. Leukapheresis sessions were performed weekly (1 hour/week) for five consecutive weeks. The leukapheresis sessions resulted in a significant improvement in the patients' clinical as well as general conditions. The abdominal pain disappeared and significant reduction of diarrhea and fecal calprotectin levels was observed. No side effects occurred. The clinical benefits were supported by resolution of ulcerative lesions. After six months of follow-up no disease relapse was observed. The leukapheresis treatment has also prevented surgical interventions in all patients enrolled in the study. Our results suggest that leukapheresis may be helpful in patients affected by inflammatory bowel diseases, allowing early reduction of immunosuppressive drug administration.

Biocompatibility of Surface-Modified Membranes for Chronic Hemodialysis Therapy.

Hemodialysis is a life-sustaining therapy for millions of people worldwide. However, despite considerable technical and scientific improvements, results are still not fully satisfactory in terms of morbidity and mortality. The membrane contained in the hemodialyzer is undoubtedly the main determinant of the success and quality of hemodialysis therapy. Membrane properties influence solute removal and the interactions with blood components that define the membrane's biocompatibility. Bioincompatibility is considered a potential contributor to several uremic complications. Thus, the development of more biocompatible polymers used as hemodialyzer membrane is of utmost importance for improving results and clinical patient outcomes. Many different surface-modified membranes for hemodialysis have been manufactured over recent years by varying approaches in the attempt to minimize blood incompatibility. Their main characteristics and clinical results in hemodialysis patients were reviewed in the present article.

Vitamin E (Alpha-Tocopherol) Metabolism and Nutrition in Chronic Kidney Disease.

Vitamin E (alpha-tocopherol) is an essential micronutrient and fat-soluble antioxidant with proposed role in protecting tissues from uncontrolled lipid peroxidation. This vitamin has also important protein function and gene modulation effects. The metabolism of vitamin E depends on hepatic binding proteins that selectively retain food alpha-tocopherol for incorporation into nascent VLDL and tissue distribution together with esterified cholesterol and triglycerides. Chronic kidney disease (CKD) is a condition of oxidative stress and increased lipid peroxidation, that are associated with alterations of alpha-tocopherol metabolism and function. Specific changes have been reported for the levels of its enzymatic metabolites, including both short-chain and long-chain metabolites, the latter being endowed with regulatory functions on enzymatic and gene expression processes important for the metabolism of lipids and xenobiotics detoxification, as well as for the control of immune and inflammatory processes. Vitamin E therapy has been investigated in CKD using both oral vitamin E protocols and vitamin E-coated hemodialyzers, showing promising results in the secondary prevention of cardiovascular disease, as well as of immune and hematological complications. These therapeutic approaches are reviewed in the present article, together with a narrative excursus on the main findings indicating CKD as a condition of relative deficiency and impaired metabolism of vitamin E.

[Nephrotoxicity induced by chemotherapy]. / Nefrotossicita' da chemioterapici.

Abnormal renal function markedly influences the clinical management of cancer patients. While the neoplasm may cause renal damage in itself, the damage may be exacerbated by treatment with chemotherapeutic agents. Since many chemotherapeutic agents are metabolized and excreted through the kidneys, their use may represent a major risk factor for the development of renal abnormalities. Moreover, when renal failure is present before chemotherapy treatment, certain drugs need dose adjustments or are not indicated. Careful monitoring of renal function during chemotherapy is thus necessary and preventive measures should be adopted when possible to reduce the occurrence of renal dysfunction.

[Management of IgA nephropathy]. / La terapia della glomerulonefrite a depositi mesangiali di IgA (IgAN).

The best treatment of IgA nephropathy (Berger's disease) is not well defined and at present no causal therapy is available. Although initially considered benign, we now recognize it as a common cause of end-stage renal disease and the natural history of IgA nephropathy is quite variable. Standard care includes angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and corticosteroids, in some cases combined with immunosuppressive drugs. The antiproteinuric and renoprotective effects of ACEIs and ARBs in IgA nephropathy have been firmly established. Treatment with corticosteroids is effective in reducing proteinuria and renal injury. The addition of cytotoxic immunosuppressive agents (cyclophosphamide and azathioprine) can be of benefit in patients with a rapidly progressive disease course. Little information is available about the clinical efficacy of tonsillectomy on long-term renal survival in patiens with IgA nephropathy; at present it cannot be recommended. The treatment of the disease is a work in progress; only better knowledge of its pathogenesis will eventually offer novel therapeutic approaches.