Portuguese Journal of Nephrology & Hypertension

The global role of kidney Transplantation: For the World Kidney Day Steering Committee 2012

World Kidney Day on March 8th 2012 provides a chance to reflect on the success of kidney transplantation as a therapy for end-stage kidney disease that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness. Anything that is both cheaper and better, but is not actually the dominant therapy, must have other drawbacks that prevent replacement of all dialysis treatment by transplantation. The barriers to universal transplantation as the therapy for end-stage kidney disease include the economic limitations which in some countries place transplantation, appropriately, at a lower priority than public health fundamentals such as clean water, sanitation and vaccination. Even in high-income countries the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients, but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical, surgical and nursing workforces with the required expertise. These problems have solutions which involve the full range of societal, professional, governmental and political environments. World Kidney Day is a call to deliver transplantation therapy to the one million people a year who have a right to benefit.

Iron isomaltoside 1000: a new high dose option for parenteral iron therapy

Iron isomaltoside 1000 (Monofer®) is a new dextran-free parenteral iron product, currently approved in 22 EU countries. Iron isomaltoside 1000 consists of iron and a carbohydrate moiety where the iron is tightly bound in a matrix structure, which enables a controlled and slow release of iron to iron-binding proteins, avoiding toxicity. The carbohydrate,isomaltoside 1000, is a purely linear chemical structure with low immunological activity. Due to the structure of iron isomaltoside 1000 and the low anaphylactic potential, there is no requirement for a test dose, and it can be administered in high doses with a maximum dosage of 20 mg/kg within 30-60 minutes in one visit. Thus, iron isomaltoside 1000 offers the broadest dosage range compared to other parenteral iron products on the market. Due to the dose flexibility, the possibility of providing full iron correction in one single visit makes iron isomaltoside 1000 highly convenient for both the health care professional and the patient. Clinical studies of iron isomaltoside 1000 show that it is an effective and well-tolerated treatment of iron deficiency anaemia with a favourable safety profile. Furthermore, iron isomaltoside 1000 does not seem to induce hypophosphataemia.

Primary glomerular diseases: variations in disease types seen in Africa and Europe

Glomerular diseases account for a significant number of patients with chronic kidney disease worldwide. IgA nephropathy (IgAN) is the predominant primary glomerular disease (PGD) seen across Europe, whereas in Africa, the prevalence of IgAN is not common. The most frequently described glomerular disease in Africa is mesangiocapillary glomerulonephritis (MCGN). The difference in the prevalence of PGDs seen in Africa and Europe may depend on several factors including genetic, socio-economic and demographic influences. Variations in exposure to infections (hygiene hypothesis) and patterns of Th1 and Th2 responses may also contribute significantly to observed differences.

The use of statins in patients with chronic kidney disease not in dialysis: A scientific review

Chronic kidney disease is a major risk factor for the incidence and severity of coronary artery disease. Patients with CKD present accelerated atherosclerosis and are prone to serious heart disease, including heart failure, before they ever reach dialysis. They have a worse cardiovascular (CV) prognosis then other patients after acute myocardial infarction (AMI), and after revascularisation. The main aim of this review article is the presentation and discussion of the best available evidence on the use of statins in patients with hyperlipidaemia and CKD not on dialysis. This paper is not based on a systematic review of the best clinical evidence on the subject of statins and CKD. It is a scientific review based on recent studies (randomised controlled trials, systematic reviews and observational studies) on risk modulation with lipid-lowering drugs in CKD. The evidence on which this paper is based was identified by searching the best available secondary sources as well as primary databases if needed. There are a series of statements that can be made on the effects of statins in patients with CKD not on dialysis. Firstly, the combination ezetimibe/simvastatin reduces AMI, non-haemorrhagic stroke and revascularisation in these patients, and a physician needs to treat less than 50 patients over four years to avoid a CV event. Secondly, the combination ezetimibe/simvastatin reduces LDL levels more than simvastatin alone. Thirdly, treatment with atorvastatin plus ACE inhibitors or ARBs may reduce proteinuria and the rate of progression of kidney disease, proteinuria and hypercholesterolaemia. Fourthly, pravastatin was associated with slower renal function decline than placebo in patients with moderate reduced GFR and proteinuria. Fifthly, simvastatin has similar effects on total cholesterol, LDL and triglyceride in CKD patients as it has in patients with normal kidney function. Sixthly, statin use is associated with reduction in albuminuria or proteinuria. Seventhly, statin therapy with rosuvastatin reduced first cardiovascular events and all-cause mortality among men and women with low LDL, elevated CRP and moderate CKD. Finally, pravastatin may not be superior to usual care in preventing end-stage renal disease and addition of atorvastatin to angiotensin-converting enzyme inhibitor or angiotensin receptor blocker may slow progression of renal disease.

Multicystic dysplastic kidney: a review of eleven years (2000 - 2010)

Introduction. Multicysticdysplastic kidney is the most common form of renal dysplasia. The natural history of multicystic dysplastic kidney is involution of the affected kidney, which justifies conservative management. The aim of this study was to evaluate the clinical course of a group of children with multicystic dysplastic kidney and compare these results with a previous study conducted 1989 -2000 in the same clinic. Patients and Methods. Retrospective analysis of the medical records of all children with multicystic dysplastic kidney referred to the paediatric nephrology unit of a tertiary paediatric hospital 2000-2010. Results. Fifty-two children (54% female) with multicystic dysplastic kidney were studied. The mean age at the time of the first visit was nineteen months with a mean follow-up time of sixty-five months. Prenatal ultrasound showed renal abnormalities in 96% of the children, 80% of which were suggestive of multicystic dysplastic kidney. All children underwent renal ultrasound and renal scintigraphy, 48 (92%) had a voiding cystourethrography and two (4%) intravenous urography. Ten (19%) children had contralateral kidney anomalies without obstruction of urinary tract, with the most frequent being pelvicalyceal dilatation (5) and vesicoureteral reflux (5). Nephrectomy was performed in five children (10%). Indications for nephrectomy were increased multicystic dysplastic kidney size in two children, ureterocele in two and bladder diverticulum in one. Of the 47 children (90%) with conservative treatment, 21 (45%) had total kidney involution (over a mean follow-up of three years). Ten (19%) children had complications, eight (15%) of them had urinary tract infection, and two proteinuria. Conclusions. As in the 1989-2000 study, prenatal ultrasound was the main form of multicystic dysplastic kidney diagnosis and contralateral kidney anomalies remain frequent (19% vs.=29%). There has been a significant reduction in the number of intravenous urographies (4% vs. 45%). Conservative treatment has been the first choice in the last few years, accompanied by a reduction in nephrectomies (10% vs. 37%). The lack of clinical problems and good evolution of children with multicystic dysplastic kidney, justifies conservative management. As these children have only one functioning kidney, an adequate monitoring with renal ultrasound and assessment of blood pressure and renal function is essential.

Clinical and pathological findings in women withFabry disease

Introduction.Fabry disease is a rare metabolic disorder caused by the genetic deficiency of the lysosomalhydrolase alpha-galactosidase A, located on chromosome X. Females with the defective gene are more than carriers and can develop a wide range of symptoms. Nevertheless, disease symptoms generally occur later and are less severe in women than in men. The enzyme deficiency manifests as aglycosphingolipidosis with progressive accumulation ofglycosphingolipids and deposit of inclusion bodies inlysosomes giving a myelinlike appearance. Patients and Methods.Records of renal biopsies performed on adults from 1st January 2008 to 31st August 2011, were retrospectively examined at the Renal Pathology Laboratory. We retrieved biopsies diagnosed withFabry disease and reviewed clinical and laboratory data and pathology findings. Results.Four female patients with a mean age of 49.3 ±4.5 (44-55) years were identified. The mean proteinuria was 0.75± 0.3 g/24h (0.4-1.2) and estimatedglomerular filtration rate (CKD EPI equation) was 71 ±15.7 ml/min/1.73m 2 (48-83). Three patients experienced extra-renal organ involvement (cerebrovascular, cardiac, dermatologic, ophthalmologic and thyroid) with distinct severity degrees. Leukocyte α-GAL A activity was below normal range in the four cases but plasma and urinary enzymatic activity was normal. Light microscopy showed predominant vacuolization of thepodocyte cytoplasm and darkly staining granular inclusions on paraffin and plastic-embedded semi-thin sections. Electron microscopy showed in three patients the characteristic myelin-like inclusions in thepodocyte cytoplasm and also focal podocyte foot process effacement. In one case the inclusions were also present in parietalglomerular cells, endothelial cells ofperitubular capillary and arterioles. Conclusion. Clinical signs and symptoms are varied and can be severe among heterozygous females with Fabry disease. Intracellular accumulation of glycosphingolipids is a characteristichistologic finding of Fabry nephropathy. Since this disease is a potentially treatable condition, its early identification is imperative. We should consider it in the differential diagnosis of any patient presenting with proteinuria and/or chronic kidney disease, especially if there is a family history of kidney disease.

Membranous nephropathy in three paediatric patients

Membranous nephropathy in childhood is usually secondary to an underlying cause. Idiopathic membranous nephropathy is a rare cause of paediatric asymptomatic proteinuria/nephrotic syndrome. We reviewed the only three cases of membranous nephropathy followed in a paediatric hospital over the last ten years. All patients were female with mean age at diagnosis of 11.3 years (10-13 years). Patients 1 and 2 presented with steroid-resistant nephrotic syndrome. Patient 3 had a history of episodes of gross haematuria, and subnephrotic-range proteinuria refractory to enalapril and losartan. All patients had normal renal function. Patient 2 had hypertension and microscopic haematuria. Patients 1 and 2 underwent renal biopsy at an average of 51.5 days after initial symptoms; in patient 3, renal biopsy was performed seven years after initial presentation with episodes of gross haematuria, and five years after discovery of proteinuria. Histopathological features indicated membranous nephropathy; in patients 2 and 3, some findings suggested the coexistence of a systemic clinical condition. Secondary causes were sought in all patients. Six months after diagnosis, patient 1 developed facial skin lesions suggestive of discoid lupus erythematosus and later had positive autoantibodies (ANA, ENA, anti-SSA). Corticosteroids and angiotensin II receptor antagonists or angiotensin converting enzyme inhibitors were given to all patients. Those with nephritic syndrome required the addition of ciclosporin to achieve remission. At the latest evaluation (mean follow-up 31.3 months), patients 1 and 3 were in remission, and patient 2 had sub-nephrotic range proteinuria as the result of poor adherence to medication. All had normal renal function and blood pressure. All were receiving treatment with prednisolone and enalapril, and patients 1 and 2 were also receiving ciclosporin. Diagnosing idiopathic membranous nephropathy in children can be challenging. At least one of our patients had atypical features suggestive of an underlying cause so may have had secondary membranous nephropathy. Follow-up must continue, even after remission, with continued monitoring for underlying systemic disease. Treatment options are angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists, corticosteroids and immunosuppressive drugs such as ciclosporin.

Atypical haemolytic-uraemic syndrome caused by factor H mutation: case report and new management strategies in children

Atypical haemolytic uraemic syndrome is caused by alternative complement pathway dysregulation. It has recently been recognised that most cases are due to genetic factors and a growing list of mutations has been described. Atypical haemolytic uraemic syndrome is associated with a dismal prognosis, a relapsing course, high acute mortality and frequent progression to end-stage renal disease. We describe a five-year-old boy admitted with a first recurrence of atypical haemolytic uraemic syndrome. The primary onset of the disease was at 15 months of age, following which there was complete recovery of haematological and renal parameters. His family history was significant in that his mother had died at the age of only 23 years of a stroke with associated thrombotic microangiopathy, suggesting a familial form of the disease. Sequencing of the gene encoding complement factor H revealed a heterozygous SCR20 mutation (3644G>T, Arg1215Leu), confirming the diagnosis. The patient was successfully treated with fresh frozen plasma infusions that induced disease remission. We also review currently evolving concepts about atypical haemolytic uraemic syndrome caused by factor H mutation, its diagnosis, the role of genetic testing and management strategies in children.

Extracorporeal shock wave lithotripsy in a 10-month-old girl with staghorn calculus

ABSTRACT Introduction: Urolithiasis is rare in developed countries. Staghorn calculi are a type of upper urinary tract stone that involves the renal pelvis and extends into at least two calyces. Although all types of urinary stones can potentially form staghorn calculi, approximately 75% are composed of a struvite matrix and are generally associated with urinary tract infection caused by urea -splitting bacteria. Curative treatment is possible only by eliminating all of the stone fragments and by eradicating urinary tract infections. Case Report: We present a case of a 10-month-old girl with a staghorn calculus caused by multiple urinary tract infections. After urine sterilisation, extracorporeal shock wave lithotripsy was performed during separate sessions. Following her last treatment, the child is free of nephrolithiasis. Conclusion: Struvite calculi should be considered in all children with Proteus urinary tract infection. Extracorporeal shock wave lithotripsy is an efficient and safe treatment in young children (<2 years) and should be considered as the first option.