Renal Failure In Adults Research Articles

Prevalence of chronic renal failure in adults in Delhi, India

Chronic renal failure (CRF) is a debilitating condition responsible for high morbidity and mortality and is a financial burden on government and society. Because of its costs and the complexity of its treatment, proper care is available to very few patients in India. A community-based study has not been done to determine the prevalence of CRF in India. We used a multi-stage cluster sampling method in the South Zones of Delhi. In each area, we first contacted the local social leader and explained the study and the medical information pamphlets. On pre-scheduled days, the study team canvassed the study zone. The individuals contacted responded to a detailed questionnaire, and had a physical examination, a dipstick urine test for albumin and sugar and a blood test for serum creatinine. A serum creatinine >1.8 mg% defined renal failure. A repeat test for serum creatinine was done after 8-12 weeks to confirm chronicity of renal failure. If it was >1.8 mg% after 3 months in the absence of reversible factors, CRF was diagnosed. The person found to have CRF was asked to attend a hospital renal clinic for further investigations and individualized management. A total of 4972 persons were contacted for the study. Their mean age was 42+/-13 years; 56% were males. Out of the 4972 who were initially approached, 4712 agreed to give the blood sample, and thus were included for the evaluation of CRF. CRF was found in 37 of them. Thus, the prevalence of CRF in that adult population was 0.785% or 7852/million. The prevalence of CRF in India makes it a serious problem in need of urgent efforts to contain it.

The cytoplasmic C-terminus of polycystin-1 increases cell proliferation in kidney epithelial cells through serum-activated and Ca 2+-dependent pathway(s)

Polycystin-1 (PC1) is a large transmembrane protein important in renal differentiation and defective in most cases of autosomal dominant polycystic kidney disease (ADPKD), a common cause of renal failure in adults. Although the genetic basis of ADPKD has been elucidated, molecular and cellular mechanisms responsible for the dysregulation of epithelial cell growth in ADPKD cysts are still not well defined. We approached this issue by investigating the role of the carboxyl cytoplasmic domain of PC1 involved in signal transduction on the control of kidney cell proliferation. Therefore, we generated human HEK293 cells stably expressing the PC1 cytoplasmic tail as a membrane targeted TrkA-PC1 chimeric receptor protein (TrkPC1). We found that TrkPC1 increased cell proliferation through an increase in cytoplasmic Ca 2+ levels and activation of PKCα, thereby upregulating D1 and D3 cyclin, downregulating p21 waf1 and p27 kip1 cyclin inhibitors, and thus inducing cell cycle progression from G0/G1 to the S phase. Interestingly, TrkPC1-dependent Ca 2+ increase and PKCα activation are not constitutive, but require serum factor(s) as parallel component. In agreement with this observation, a significant increase in ERK1/2 phosphorylation was observed. Consistently, inhibitors specifically blocking either PKCα or ERK1/2 prevented the TrkPC1-dependent proliferation increase. NGF, the TrkA ligand, blocked this increase. We propose that in kidney epithelial cells the overexpression of PC1 C-terminus upregulates serum-evoked intracellular Ca 2+ by counteracting the growth-suppression activity of endogenous PC1 and leading to an increase in cell proliferation.

Clinical diabetic nephropathy in a tropical African population.

Diabetic nephropathy is the single most important disorder leading to renal failure in adults in the Western countries and it is among the first three major causes of end stage renal disease in Nigeria. The aim of this study is to show the features of clinical diabetic nephropathy in the Olabisi Onabanjo University Teaching Hospital, Ogun State, Nigeria. The study group consists of 342 consecutive diabetic patients with persistent proteinuria (positive albustix) and diabetic retinopathy, seen from January 2000 to June 2001 in the Ogun State University Teaching Hospital, Sagamu. Clinical and laboratory parameters were recorded. Students' t-test and Spearman correlation coefficient were used in analysis. The frequency of occurrence of clinical diabetic nephropathy is 28.4% with majority already symptomatic despite normal biochemistry. Mean ages of type 1 and type 2 are 26+/-7.9 years and 53.4+/-6.3 years respectively with a sex ratio of 1.2:1. Mean duration of disease is 6.5+/-3.6 years and 9.4+/-4.1 years respectively. Two hundred and seventy-one (79.2%) patients were hypertensive. Nephrotic syndrome is not a common presentation. Diabetic nephropathy is a significant problem in this environment.

Successful treatment of crescentic glomerulonephritis associated with adult-onset Henoch-Schoenlein purpura by double-filtration plasmapheresis

Henoch-Schoenlein purpura (HSP) crescentic glomerulonephritis with acute renal failure in adults is extremely rare. The condition carries a grave renal outcome if it is not appropriately managed. Oral corticosteroids, intravenous methylprednisolone pulse therapy and plasmapheresis with concomitant plasma replacement have been used alone or in various combinations to treat patients with HSP nephritis, yet the effects are uncertain. We describe a 33-year-old man with oliguric acute renal failure in the setting of HSP crescentic glomerulonephritis that is refractory to intravenous methylprednisolone pulse therapy (1,000 mg/day for 3 days) with maintained oral prednisolone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day) for 3 weeks, resulting in successful recovery of renal function after 9 sessions of simple double-filtration plasmapheresis treatment without concomitant plasma replacement. There was no recurrence of vasculitic events within 18 months. In this case, we emphasize that simple double-filtration plasmapheresis without concomitant plasma replacement is an effective and safe modality therapy for adult patients with HSP crescentic glomerulonephritis and acute renal failure, especially when conventional therapy has failed.

Emerging drugs for renal failure

Renal failure involves a significant impairment of the essential functions of the kidney, which can be either acute with sudden and rapid onset (acute renal failure [ARF]) or chronic with gradual onset (chronic renal failure [CRF]). ARF, if detected early, may be halted or reversed, whereas CRF is generally irreversible. Without treatment or intervention, both forms of renal failure lead to end stage renal failure (ESRF) or end stage renal disease (ESRD), requiring renal replacement therapy (RRT) in the form of dialysis or renal transplantation for survival. However, provision of RRT requires expert teams working in specialised units, making therapy of patients with renal failure expensive; furthermore, RRT is complex, with its own complications. Although pharmacological interventions have shown promise in experimental models, these have not been as successful in the clinical setting (e.g., administration of atrial natriuretic peptide, low-dose dopamine). At present, drugs are administered during CRF to either reduce one of the many risk factors of CRF (e.g., angiotensin-converting enzyme inhibitors, statins) or to deal with the consequences of CRF (e.g., erythropoietin, calcitriol). Recent evidence suggests that some of these interventions may provide further direct beneficial effects via reduction of renal inflammation. Although these interventions have greatly improved the prospects for patients suffering ESRF, the development of novel drugs and therapies with which to reduce the consequences of renal failure and ESRD remain topics of great interest. This article reviews the therapies available for the prevention and management of renal failure in adults and describes, in detail, emerging drugs and novel interventions that may soon become available for the treatment or prevention of ESRF.

Three novel COL4A4 mutations resulting in stop codons and their clinical effects in autosomal recessive Alport syndrome.

Autosomal recessive Alport syndrome is caused by mutations in the COL4A3 and COL4A4 genes which code for the alpha3 and alpha4 chains of type IV collagen. These mutations result in haematuria, progressive renal impairment and often hearing loss, lenticonus and retinopathy. We describe here the mutations demonstrated by screening the 47 coding exons of the COL4A4 gene in six families with autosomal recessive Alport syndrome using PCR-single stranded conformational polymorphism (SSCP) analysis. Six sequence variants were identified. These included three novel mutations (2846delG, 2952delG and S969X) in exons 30 - 32 that all resulted in premature stop codons. These mutations were demonstrated in the heterozygous form in 3 families, and the S969X mutation was also present in the homozygous form in one of the two consanguinous families. These three mutations accounted for 40% (4/10) of the total mutant alleles in the six families studied. Six of the seven (86%) individuals with autosomal recessive Alport syndrome who had these mutations in the compound heterozygous or homozygous forms developed renal failure in adulthood, as well as hearing loss and ocular abnormalities. Haematuria was present in 15 of the 17 (88%) heterozygous mutation carriers. The other non-pathogenic sequence variants noted in COL4A4 included a nonglycine missense variant (L1004P), an intronic variant (4731-8 T>C) and a neutral polymorphism (V1516V).

Maladie de Fabry (déficit en alpha-galactosidase A) : Physiopathologie, signes cliniques et aspects génétiques

Fabry disease (FD, OMIM 301500) is an X-linked inherited disorder of metabolism due to mutations in the gene encoding alpha-galactosidase A, a lysosomal enzyme. The enzymatic defect leads to the accumulation of neutral glycosphingolipids throughout the body, particularly within endothelial cells. Resulting narrowing and tortuosity of small blood vessels lead to tissue ischaemia and infarction. Inability to prevent the progression of glycosphingolipid deposition causes significant morbidity (acroparesthesia, angiokeratoma, autonomic dysfunction, cardiomyopathy and deafness), and mortality from early onset strokes, heart attack and renal failure in adulthood. Demonstration of alpha-galactosidase A deficiency in leukocytes or plasma is the definitive method for the diagnosis of affected hemizygous males. Most heterozygotes present with a cardiac, renal or neurological symptomatology, although to a lesser extent than what is observed in hemizygotes. Due to random X-chromosomal inactivation, enzymatic detection of carriers is often inconclusive. Molecular testing of possible carriers is therefore mandatory for accurate genetic counselling. The GLA gene has been cloned and more than 200 mutations have been identified. Medical management is symptomatic and consists of partial pain relief with analgesic drugs (gabapentin, carbamazepine), whereas renal transplantation or dialysis is available for patients experiencing end-stage renal failure. However, the ability to produce high doses of alpha-galactosidase A in vitro has opened the way to clinical studies and enzyme replacement therapy has recently been validated as a therapeutic agent for FD patients in clinical trials. Long term safety and efficacy of replacement therapy are currently being investigated.

Maladie de Fabry (déficit en α-galactosidase A) : innovations thérapeutiques récentes

Fabry disease (FD, OMIM 301500) is an X-linked inherited disorder of metabolism due to mutations in the gene encoding alpha-galactosidase A, a lysosomal enzyme. The enzymatic defect leads to the accumulation of neutral glycosphingolipids throughout the body, particularly within endothelial cells. Resulting narrowing and tortuosity of small blood vessels with endothelial dysfunction lead to tissue ischaemia and infarction. Inability to prevent the progression of glycosphingolipid deposition causes significant morbidity and mortality from early onset strokes, cardiomyopathy and renal failure in adulthood. Medical management is symptomatic and consists of partial pain relief with analgesic drugs (gabapentin, carbamazepine), antihypertensive drugs, whereas renal transplantation or dialysis is available for patients experiencing end-stage renal failure. However, the ability to produce high doses of alpha-galactosidase A in vitro has opened the way to preclinical studies in the mouse model, and to the development of the first clinical trials in patients with Fabry disease. Enzyme replacement therapy has recently been validated as a therapeutic agent for Fabry disease patients. Long term safety and efficacy of replacement therapy are currently being investigated. Substrate deprivation and gene therapy may also prove future alternative therapeutic options.

Pronóstico en la vida adulta de la nefropatía igA diagnosticada en la edad pediátrica

To evaluate long-term prognosis in a group of children with IgA nephropathy and to analyse which clinical factors were associated with progression to chronic renal failure in adulthood. Retrospective study. 58 young adults with IgA nephropathy diagnosed at 10.6(SD 2.9) years old and studied after a follow-up of 11.8 (SD 2.9) years. Relapses of macroscopic hematuria and proteinuria were the most frequent symptoms at onset (75.9%). In 25.9% of patients high plasmatic IgA levels were also detected. Most cases had grade I (44.8%)or grade II (44.8%) histological lesions at diagnosis. At the last control, clinical remision was observed in 21 patients (36.2%) and 50% of the whole group remained with abnormal urine. 8 patients(13.8%) reached terminal renal failure. Mean renal survival (defined as glomerular filtration rate above 50 ml/min/1.73 m2)was 100, 93.3 and 81.1% at 5, 10 and 15 years of evolution, respectively. About 14% of children with IgA nephropathy had long-term renal bad prognosis. Hypertension at onset, plasma creatinine elevation and proteinuria during adolescence were significant risk factors associated with chronic renal failure during adulthood. Minimal lesions at IgA nephropathy diagnosis in children did not exclude long-term poor prognosis.

Hemolytic uremic syndrome. Recurrence after renal transplantation. Groupe Coopératif de l'Ile-de-France (GCIF).

Hemolytic uremic syndrome (HUS) is an uncommon cause of end-stage renal failure in adults, and few data are available concerning the outcome of renal transplantation in these patients. We conducted this retrospective multicentric study to appreciate the outcome of adult renal transplant recipients whose primary disease was HUS. Sixteen patients, transplanted between 1975 and 1995, were included in the study. In each case, initial diagnosis of HUS was documented by a kidney biopsy. These 16 patients received a total of 25 allografts: 1 graft for 9 patients, 2 grafts for 5 patients, and 3 grafts for 2 patients. Nine patients (56%) developed definite clinical and pathologic evidence of recurrence on at least 1 graft. Four additional patients (25%) demonstrated only some clinical or pathologic evidence of recurrence which could not be distinguished from acute vascular rejection. Three patients had no sign of recurrence of the initial disease. The 1-year graft survival rate was 63% and the 5-year graft survival rate was 18.5%. In the group of patients with proven or possible recurrence (n = 13), the 1-year and 5-year graft survival rates were 49% and less than 10%, respectively. The recurrence was an early event, occurring before the end of the first month after transplantation in half the cases. The recurrence rate was 92% in non-nephrectomized patients and 50% in patients with bilateral nephrectomy. In the literature, 71 adult patients with primary HUS had received a total of 90 kidney grafts. Among them, 54% had a recurrence on their graft, which was diagnosed in 52% of the kidney transplants. It is note-worthy that when data from the literature are pooled with our results, the rate of recurrence appears to be significantly lower in binephrectomized patients than in patients with their native kidneys at the time of transplantation (5 of 14 versus 27 of 35 patients, respectively, p = 0.0155). By univariate analysis, no other risk factor for recurrence could be identified. Treatment with cyclosporine A did not influence the recurrence rate. We conclude that recurrence of HUS after renal transplantation is a frequent, early, and severe complication, leading rapidly to graft loss. Prospective studies are needed to confirm that bilateral nephrectomy prior to transplantation decreases the rate of recurrence.

The polycystins: a novel class of membrane-associated proteins involved in renal cystic disease.

Polycystin-1, polycystin-2 and polycystin-L are the predicted protein products of the PKD1, PKD2 and PKDL genes, respectively. Mutations in PKD1 and PKD2 are responsible for almost all cases of autosomal dominant polycystic kidney disease (ADPKD). This condition is one of the commonest mendelian disorders of man with a prevalence of 1:800 and is responsible for nearly 10% of cases of end-stage renal failure in adults. The cloning of PKD1 and PKD2 in recent years has provided the initial steps in defining the mechanisms underlying renal cyst formation in this condition, with the aim of defining pharmacological and genetic interventions that may ameliorate the diverse and often serious clinical manifestations of this disease. The PKD genes share regions of sequence similarity, and all predictintegral membrane proteins. Whilst the predicted protein domain structure of polycystin-1 suggests it is involved in cell-cell or cell-matrix interactions, the similarity of polycystin-2 and polycystin-L to the pore-forming domains of some cation channels suggests that they all form subunits of a large plasma membrane ion channel. In the few years since the cloning of the PKD genes, a consensus that defines the range of mutations, expression pattern, interactions and functional domains of these genes and their protein products is emerging. This review will therefore attempt to summarise these data and provide an insight in to the key areas in which polycystin research is unravelling the mechanisms involved in renal cyst formation.

The role of cell adhesion molecules in ischemic acute renal failure

Ischemia remains the primary cause of acute renal failure in adults. Following the development and practical application of dialysis, little progress has been made in the treatment of ischemic acute renal failure (ARF) to significantly affect patient outcome. However, excellent advancement has occurred in the understanding of the cellular consequences of ischemic injury. This has occurred through an integrated approach using complementary in vivo and in vitro models of ischemic cell injury. Fundamental insights into the physiology, biochemistry, cell biology, and molecular biology of ischemic cell injury have now resulted in new clinical trials and renewed optimism. These combined basic science and clinical research approaches to design and test new therapies were recently reviewed to identify priorities by a NIH supported conference ( 1 Dubose Jr, T.D Warnock D.G Mehta R.L et al. Acute renal failure in the 21st century recommendations for management and outcomes assessment. Am J Kidney Dis. 1997; 29: 793-799 Abstract Full Text PDF PubMed Scopus (90) Google Scholar ). Since substantial progress has been made in the pathophysiologic aspects of cell adhesion molecules in the injury and recovery phases of ischemic ARF, the purpose of this review is to delineate and synthesize these findings. Although brief introductions will be given to the different classes of cell adhesion molecules (CAMs), the reader is referred to the original article in this series, which dealt exclusively with the structure and cellular function of these molecules ( 2 Kypta R.M Su H Reichardt L.F Association between a transmembrane protein tyrosine phsophatase and the cadherin-catenin complex. J Cell Biol. 1996; 134: 1519-1529 Crossref PubMed Scopus (234) Google Scholar ).

End-stage renal failure in adults with the tuberous sclerosis complex

Tuberous sclerosis (TSC) is a multisystem disorder encompassing a wide spectrum of pathological renal lesions. Renal involvement is commonly asymptomatic but can result in significant morbidity, and renal failure has been reported. The risk of renal failure in patients with TSC in the UK has not been defined. A survey of the 170 members of the European Dialysis and Transplant Association was carried out to identify and collect clinical information on patients with TSC in their renal replacement programme. Ten patients were identified as having end-stage renal failure (ESRF) and TSC, giving an incidence of 1% in patients with TSC and normal intellect. There was a wide spectrum of underlying pathology and clinical presentation within this group. ESRF is rare in TSC but does contribute to significant morbidity and mortality in this group.

Acute renal failure: role of dialysis membrane biocompatibility.

Recent clinical studies of acute renal failure in adults have focused attention on the biocompatibility of the dialysis membrane as a possible factor influencing patient morbidity and mortality. In this article, we review the concept of dialysis membrane biocompatibility and highlight the difficulty of finding an ideal definition. We then expand on the possible roles of complement and neutrophil activation by dialysis membranes, which may prolong the recovery from acute renal failure. The results of several clinical studies analyzing the impact of dialysis membranes on the course and outcome of acute renal failure are discussed. Finally, the possible relevance of biocompatibility in continuous renal replacement therapies is emphasized.

Renal transplantation in adults with thrombotic thrombocytopenic purpura/haemolytic-uraemic syndrome

Thrombotic thrombocytopenic purpura/haemolytic-uraemic syndrome (TTP/HUS) is a rare cause of renal failure in adults. There is little data concerning the outcome of adult patients who receive a renal transplant for TTP/HUS: We have carried out a survey of 22 transplant centres in the USA to determine the outcome of patients who developed ESRD from TTP/HUS and latter received a renal transplant. Twelve of the 22 centres responded to our inquiry. Seven centres had not transplanted any patients with TTP/HUS, and five centres had transplanted a total of 24 grafts in 17 patients with TTP/HUS: Thirty-three per cent of patients demonstrated definite clinical and pathological evidence of recurrence of TTP/HUS: An additional 16% of patients demonstrated pathological evidence of possible recurrence of TTP/HUS in the absence of clinical manifestations. The overall 1-year graft survival rate was 42% and the 2-year graft survival rate was 35%. In our experience recurrence TTP/HUS was associated with universal graft failure. Although cyclosporin A does occasionally cause a thrombotic angiopathy in patients with no history of TTP/HUS, we found no evidence that it should be avoided in patients with a previous history of ESRD from TTP/HUS who subsequently receive a renal transplant. TTP/HUS frequently recurres in adults who receive a renal transplant, with a 2-year graft survival rate of 35%.

Acute Renal Failure

Acute renal failure is characterized by a deterioration of renal function over a period of hours to days, resulting in the failure of the kidney to excrete nitrogenous waste products and to maintain fluid and electrolyte homeostasis. In the past five decades, several important causes of acute renal failure and the pathophysiologic mechanisms that underlie renal dysfunction have come to be understood. In this article we highlight the epidemiology, general causes, and evaluation of acute renal failure in adults. We then expand on the pathophysiology of ischemic acute renal failure and discuss the rationale for both current and future therapies. . . .

Bone Measurements in Renal Failure in Adults

The ideas about the stability and conservatism of the osteoarticular system, its weak reaction to metabolic disorders are becoming a thing of the past. The human skeleton becomes an arena where dystrophic processes occur as a result of, for example, diseases of the blood [13], abdominal organs [3]. All these phenomena have a complex genesis and were previously observed much less frequently. As the diagnosis and treatment of the main diseases of osteodystrophy of this origin improves, they are encountered more and more often, but they are not well covered in the literature, and discrepancies are observed even in the names of the syndromes. So, shifts in the musculoskeletal system (ODS) in congenital lesions of the renal tubules are defined as the Debreu de Toni Fanconi [1], de Toni Fanconi [5], de Toni Debre Fanconi [6], Fanconi syndromes de Toni-Debre [8]. Insufficient attention to the problem of renal osteodystrophies (RO), especially in adults, prompted the authors to write this review.

Fatal Cutaneous Necrosis Mimicking Calciphylaxis in a Patient With Type 1 Primary Hyperoxaluria

Cutaneous necrosis of the proximal lower extremities in a patient with end-stage renal disease is the classic presentation of calciphylaxis, an untreatable, rare, generally fatal necrotizing cutaneous syndrome. Type 1 primary hyperoxaluria (PH-1) usually presents in childhood with recurrent urolithiasis. Since enzymatic studies to confirm the metabolic defect are now available, some cases of idiopathic renal failure in adulthood have been shown to be caused by PH-1. These patients may develop vascular oxalate deposits resulting in livedo reticularis and distal acral vascular insufficiency. We describe a patient who presented in end-stage renal failure with proximal lower extremity cutaneous necrosis suggestive of calciphylaxis. A cutaneous biopsy specimen revealed oxalate crystals within blood vessels, and a diagnosis of PH-1 was confirmed enzymatically. This patient illustrates that PH-1 may present in adulthood, and, in the setting of cutaneous necrosis associated with end-stage renal disease, it may be confused with calciphylaxis. The importance of making a diagnosis of PH-1 is the potential ability to achieve long-term survival by reversing the underlying metabolic defect with hepatic transplantation.

Mapping the gene causing X-linked recessive nephrolithiasis to Xp11.22 by linkage studies.

X-linked recessive nephrolithiasis is associated with kidney stones and renal tubular dysfunction in childhood progressing to renal failure in adulthood. The primary defect causing this renal tubular disorder is unknown and determining the chromosomal location of the mutant gene would represent an important step toward defining the biochemical basis. We have performed linkage studies in 102 members (10 affected males, 47 unaffected males, 15 obligate heterozygote females, and 30 unaffected females) from five generations of one family. As genetic markers we used 10 cloned human X chromosome fragments identifying restriction fragment length polymorphisms and seven pairs of oligonucleotide primers identifying microsatellite polymorphisms. Linkage with the locus DXS255 was established with a peak LOD score = 5.91 at 3.6% recombination, thereby localizing the X-linked recessive nephrolithiasis gene to the pericentromeric region of the short arm of the X chromosome (Xp11.22). Multilocus analysis indicated that the mutant gene was distal to DXS255 but proximal to the Duchenne muscular dystrophy locus on Xp. Thus, the gene that causes X-linked recessive nephrolithiasis maps to the pericentromeric region of the short arm of the X chromosome (Xp11.22), and further characterization of this gene will help to elucidate the factors controlling renal tubular function and mineral homeostasis.

Incidence of severe acute renal failure in adults: results of a community based study.

To determine the age related incidence of severe acute renal failure in adults in two health districts in England. Prospective study of patients identified as having severe acute renal failure within a two year period; subsequent monitoring of outcome for a further two years. Two health districts in Devon. Those adults in a population of 444,971 who developed severe acute renal failure (serum creatinine concentration > 500 mumol/l) for the first time during two years, with subsequent fall of the serum creatinine concentration below the index value. 125 adults (140 per million total population yearly, 172 per million adults) developed severe acute renal failure, of whom 90 (72%) were over 70. Age related incidence rose from 17 per million yearly in adults under 50 to 949 per million yearly in the 80-89 age groups. In 31 patients (25%) the cause was prostatic disease, which was related to a good prognosis (84% (26) alive at three months). Overall survival was 54% (67) at three months and 34% (42) at two years and was not significantly age related. 18 per million total population yearly (22 per million adult population) received acute dialysis. Referral rate for specialised opinion was 51 per million total population yearly with an estimated appropriate referral rate of 70 per million per year. The incidence of severe acute renal failure in the community is at least twice as high as the incidence reported from renal unit based studies. Prostatic disease, a preventable and treatable problem, is the most common cause. Survival figures indicate that age alone should not be a bar to specialist referral or treatment.