Pretransplant nephrectomy in patients with autosomal dominant polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and a frequent cause of end-stage renal failure. Transplantation in patients with ADPKD is associated with specific cyst-related problems, especially urinary tract infections (UTI). Although pretransplant nephrectomy has been applied in this group of patients, evidence of the benefits of this strategy is lacking. Therefore, we compared the outcomes and posttransplant complications among patients with or without pretransplant nephrectomy. PATIENTS AND METHODS: ADPKD patients (73) transplanted from cadaveric donors were reviewed retrospectively with regard to posttransplant complications and outcomes. The groups either underwent pretransplant unilateral nephrectomy (n = 30) or were transplanted with native kidneys intact (n = 43). RESULTS: Two patients underwent simultaneous bilateral nephrectomy due to a large size of the polycystic kidneys interfering with the transplant operation. Overall postransplant complications were more frequent in the group without nephrectomy (34% vs 20%); however, the difference was not statistically significant. Most complications were related to cyst infections with 3 deaths (12%) due to lethal septicemia in the group without nephrectomy. No infection-related deaths were noted in the group with pretransplant nephrectomy. CONCLUSIONS: Graft and patient outcomes as well postransplant complications were similar in both groups, independent of previous nephrectomy. It seems that pretransplant unilateral nephrectomy should not be routine and has no advantage over transplantation with both native kidneys intact, although this conclusion is limited by the small number of patients. An Individualized approach should be applied especially when there has been a history of cyst-related infection.     

Boy with autosomal recessive polycystic kidney and autosomal dominant polycystic liver disease

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) shows a great phenotypic variability between patients, ranging from perinatal demise to mildly affected adults. Autosomal dominant polycystic liver disease (PCLD) does not manifest in childhood. CASE-DIAGNOSIS/TREATMENT: A boy was reported with the co-occurrence of ARPKD and PCLD. He presented at the age of 16 days with pyelonephritis and urosepsis. Subsequent investigations showed enlarged kidneys and hyperechogenic renal medulla and liver parenchyma. Genetic analysis revealed compound heterozygous mutations in the PKHD1 gene (p.Arg496X and p.Ser1862Leu). After his mother was diagnosed with PCLD, the finding of a liver cyst on ultrasound prompted analysis of the PRKCSH gene, revealing a missense mutation (p.Arg139His). At the most recent follow-up at 13 years of age, the patient's course and clinical examination was uneventful with normal renal and liver function without evidence of portal hypertension. CONCLUSIONS: The patient with ARPKD and PCLD has so far demonstrated a benign clinical outcome, consistent with the great phenotypic variability of ARPKD and, apart from the liver cyst, asymptomatic manifestation of PCLD in childhood. However, close long-term follow-up is mandatory.     

Clinical problems in hemodialysis patients with autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD ) is a common monogenic disease characterized by massive enlargement of fluid‐filled cysts in the kidney. Due to its genetic pattern, the disease differs from other CKD. ADPKD is a multi‐system, progressive disorder which is frequently complicated with hypertension, cardiovascular events and cerebrovascular disease. Thus, there are many clinical problems specific to ADPKD . In this article, we reviewed these clinical problems and their management in ADPKD with hemodialysis patients.     

Native nephrectomy in transplant patients with autosomal dominant polycystic kidney disease

INTRODUCTION

This study examined the clinical indications and timing for native nephrectomy (NN), together with the associated pathological findings in transplant patients with autosomal dominant polycystic kidney disease (ADPKD) at our institute over a period of 20 years.

METHODS

A retrospective review was performed of ADPKD patients who had undergone both kidney transplantation and NN. Patients were identified from the kidney transplant database between 1988 and 2008 at Guy''s and St Thomas'' Hospital and the notes reviewed. All NN specimens were re-reviewed and reported according to current guidelines.

RESULTS

There were 157 kidney transplants performed for ADPKD (114 cadaveric and 43 living donor). Of these, 31 required NN (28 bilateral). The timing of NN was pre-transplant in 10 cases, at the time of the transplant in 1 case and post-transplant in 20 cases. The indications for NN were urinary tract infection (n=14, 45%), pain (n=12, 39%), tumour suspicion (n=3, 10%), haematuria (n=1, 3%) and space (n=1, 3%). Mortality in this NN series was 3%, with a 65% surgical morbidity rate. The length of hospital stay post-NN was significantly longer with open compared with laparoscopic techniques (p=0.003). There were two renal cell carcinomas (RCCs) in this series. Both patients presented with macroscopic haematuria (bilateral pT1a papillary RCCs in one case and a pT3b clear cell RCC in the other case). The incidence of RCC in this series of ADPKD transplant patients was 1.3%.

CONCLUSIONS

We have demonstrated that the majority of ADPKD patients do not require NN, with only 20% of our series undergoing this procedure. The timing of NN is variable and dictated by indication. NN was only required to make space for transplantation in one case (combined kidney and pancreas transplant). The main indications for NN were recurrent infection and pain, where NN can provide a successful outcome. Laparoscopic NN can be performed safely in patients with ADPKD. Haematuria in such patients should not be assumed to be of benign origin and requires exclusion of urinary tract malignancy as the incidence of RCC in this population is at least as common as in the general population.     

Acute conditions after kidney transplantation in patients with autosomal dominant polycystic kidney disease

There is a high risk of severe complications after kidney transplantation. In patients with autosomal dominant polycystic kidney disease (AD-PKD) the incidence of complications like ischaemic cardiac disease, acute myocardial infarction, pulmonary embolism, perforation of colonic diverticulosis is especially higher. The authors want to indicate another specific complication, rupture of the cyst of own polycystic kidney with retroperitoneal haemorrhage. Within the group of 658 patients who underwent kidney transplantation between January 1981 and January 2000 there were 54 (8.2%) patients with AD-PKD. Four patients with severe retroperitoneal haemorrhage due to rupture of the cyst of own polycystic kidney we present in a short case reports. All cases were fatal. Expect morphologic and functional follow up of the graft it is necessary to follow up polycystic kidney and indicate urgent nephrectomy in the case of any change.     

Optimal care of autosomal dominant polycystic kidney disease patients

Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening, hereditary disease. The prevalence of ADPKD is more common than Huntington disease, haemophilia, sickle cell disease, cystic fibrosis, myotonic dystrophy and Down syndrome combined. In recent years there have not only been advances in the understanding of the genetic and molecular events involved in ADPKD, but some diagnostic and therapeutic advances have also emerged. In the genetics area, the gene for PKD1 was localised to chromosome 16, is associated with polycystin-2 protein, and found to account for approximately 85% of patients with ADPKD. The gene for PKD2, found in chromosome 4, accounts for approximately 15% of ADPKD, and is associated with the polycystin-2 protein. While these genetic and molecular biology findings have stimulated a great deal of exciting basic research in ADPKD, therapies to decrease morbidity and mortality in ADPKD patients have yet to emerge from these findings. In contrast, the early diagnosis and treatment of hypertension with inhibitors of the renin-angiotensin-aldosterone system have the potential to decrease or prevent left ventricular hypertrophy cardiac complications and slow the progression of the renal disease.     

Hypertension in autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) has been shown to be associated with a greater than 50 percent incidence of hypertension prior to deterioration in renal function as assessed by glomerular filtration rate. The present study provides evidence for increased cardiac pre-load, as assessed by plasma atrial natriuretic factor (ANF) and cardiac index, in hypertensive as compared to normotensive ADPKD. The hypertensive ADPKD patients exhibited an increased renal vascular resistance as compared to the normotensive patients in spite of comparable glomerular filtration rates. It is hypothesized that the renal involvement of hypertensive ADPKD patients causes an impaired renal response to the observed increase in cardiac index, and also may release a venoconstrictor (such as angiotensin) which contributes to the enhanced cardiac pre-load and thus the hypertension.     

Angiogenesis and autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the growth of multiple cysts that in many cases result in end-stage renal disease. Current strategies to reduce cyst progression in ADPKD focus on modulating cell turnover, fluid secretion, and vasopressin signalling; but an alternative approach may be to target pathways providing “general support” for cyst growth, such as surrounding blood vessels. This could be achieved by altering the expression of growth factors involved in vascular network formation, such as the vascular endothelial growth factor (VEGF) and angiopoietin families. We highlight the evidence that blood vessels and vascular growth factors play a role in ADPKD progression. Recent experiments manipulating VEGF in ADPKD are described, and we discuss how alternative strategies to manipulate angiogenesis may be used in the future as a novel treatment for ADPKD.     

Ambulatory blood pressure in hypertensive patients with autosomal dominant polycystic kidney disease

Background: Ambulatory blood pressure is more closely correlated with various indices of hypertensive target-organ damage, and is a better prognostic predictor of cardiovascular morbidity and mortality than conventional methods of blood pressure measurement. Autosomal dominant polycystic kidney disease (ADPKD) is complicated by hypertension, progressive renal failure, and an increased risk of cardiovascular mortality. This study investigated the 24-h ambulatory blood pressure profile in patients with ADPKD in view of the sparsity of such data in these patients and the possibility that abnormal diurnal blood pressure variations may have prognostic consequences. Methods: Ambulatory blood pressure was measured over a 24-h period by the oscillometric method with an automatic non-invasive recorder (SpaceLabs 90207 system) in matched groups of 25 hypertensive patients with ADPKD and 25 patients with essential hypertension. Results: Both groups showed a nocturnal decrease in blood pressure, but this was significantly smaller in patients with ADPKD. There was no evidence of enhanced lability of blood pressure in ADPKD. Conclusion: The nocturnal fall in blood pressure was attenuated in patients with ADPKD. Further studies are required to assess the importance of this finding and its possible contribution to the progression of renal failure or increased cardiovascular mortality in these patients.     

Cyst sclerotherapy with minocycline hydrochloride in patients with autosomal dominant polycystic kidney disease

BACKGROUND: The enlarged cysts in autosomal dominant polycystic kidney disease(ADPKD) frequently cause abdominal discomfort. Cyst sclerotherapywith minocycline hydrochloride was performed to relieve thissymptom. METHODS: Ten symptomatic ADPKD cases were recruited. As a sclerosant,minocycline hydrochloride solution (10 mg/dl) was used. Thissolution was instilled into the cysts under ultrasonographiccontrol. Renal volume was calculated before therapy and at 6-monthintervals thereafter. Renal function and blood pressure wereregularly monitored. The effect of sclerotherapy on symptomswas also assessed at 6-month intervals. RESULTS: At 6 months, renal volume was statistically lower than the presclerotherapy,and was associated with improvement in chronic symptoms. However,such ameliorating effects were blunted at 12 months. Renal volumereduction at 6 and 12 months showed a significant positive correlationwith the dose of minocycline injected. No significant influencein renal function and blood pressure was observed. CONCLUSIONS: These results suggest that cyst sclerotherapy with minocyclinehydrochloride is a valid treatment regime for the relief ofchronic symptoms in ADPKD cases, although repeated applicationof this approach may be required to obtain a more long-termeffect.     

Genotype-phenotype correlations in autosomal dominant and autosomal recessive polycystic kidney disease

The phenotypes that are associated with the common forms of polycystic kidney disease (PKD)--autosomal dominant (ADPKD) and autosomal recessive (ARPKD)--are highly variable in penetrance. This is in terms of severity of renal disease, which can range from neonatal death to adequate function into old age, characteristics of the liver disease, and other extrarenal manifestations in ADPKD. Influences of the germline mutation are at the genic and allelic levels, but intrafamilial variability indicates that genetic background and environmental factors are also key. In ADPKD, the gene involved, PKD1 or PKD2, is a major factor, with ESRD occurring 20 yr later in PKD2. Mutation position may also be significant, especially in terms of the likelihood of vascular events, with 5' mutations most detrimental. Variance component analysis in ADPKD populations indicates that genetic modifiers are important, but few such factors (beyond co-inheritance of a TSC2 mutation) have been identified. Hormonal influences, especially associated with more severe liver disease in female individuals, indicate a role for nongenetic factors. In ARPKD, the combination of mutations is critical to the phenotypic outcome. Patients with two truncating mutations have a lethal phenotype, whereas the presence of at least one missense change can be compatible with life, indicating that many missense changes are hypomorphic alleles that generate partially functional protein. Clues from animal models and other forms of PKD highlight potential modifiers. The information that is now available on both genes is of considerable prognostic value with the prospects from the ongoing genetic revolution that additional risk factors will be revealed.     

Retinitis pigmentosa associated with autosomal dominant polycystic kidney disease

SUMMARY: We report a case of a 35-year-old man with autosomal dominant polycystic kidney disease (ADPKD) who presented for the first time with end-stage renal failure. He had a long history of blurred vision and on examination had retinitis pigmentosa. to our knowledge, this is the second report on the association of retinitis pigmentosa with polycystic kidney disease.     

Improvement of endothelial dysfunction with simvastatin in patients with autosomal dominant polycystic kidney disease

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