Adult Dominant Polycystic Kidney Disease Research Articles

Wall Tension and Tubular Resistance in Kidney Cystic Conditions.

The progressive formation of single or multiple cysts accompanies several renal diseases. Specifically, (i) genetic forms, such as adult dominant polycystic kidney disease (ADPKD), and (ii) acquired cystic kidney disease (ACKD) are probably the most frequent forms of cystic diseases. Adult dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by multiple kidney cysts and systemic alterations. The genes responsible for the condition are known, and a large amount of literature focuses on the molecular description of the mechanism. The present manuscript shows that a multiscale approach that considers supramolecular physical phenomena captures the characteristics of both ADPKD and acquired cystic kidney disease (ACKD) from the pathogenetic and therapeutical point of view, potentially suggesting future treatments. We first review the hypothesis of cystogenesis in ADPKD and then focus on ACKD, showing that they share essential pathogenetic features, which can be explained by a localized obstruction of a tubule and/or an alteration of the tubular wall tension. The consequent tubular aneurysms (cysts) follow Laplace's law. Reviewing the public databases, we show that ADPKD genes are widely expressed in various organs, and these proteins interact with the extracellular matrix, thus potentially modifying wall tension. At the kidney and liver level, the authors suggest that altered cell polarity/secretion/proliferation produce tubular regions of high resistance to the urine/bile flow. The increased intratubular pressure upstream increases the difference between the inside (Pi) and the outside (Pe) of the tubules (∆P) and is counterbalanced by lower wall tension by a factor depending on the radius. The latter is a function of tubule length. In adult dominant polycystic kidney disease (ADPKD), a minimal reduction in the wall tension may lead to a dilatation in the tubular segments along the nephron over the years. The initial increase in the tubule radius would then facilitate the progressive expansion of the cysts. In this regard, tubular cell proliferation may be, at least partially, a consequence of the progressive cysts' expansion. This theory is discussed in view of other diseases with reduced wall tension and with cysts and the therapeutic effects of vaptans, somatostatin, SGLT2 inhibitors, and potentially other therapeutic targets.

Diet and Physical Activity in Adult Dominant Polycystic Kidney Disease: A Review of the Literature.

Autosomal polycystic kidney disease is the most common inherited kidney disease determining 5% of all end-stage kidney disease. The only therapy approved for this condition is Tolvaptan, which, with its aquaretic effect, has a strong effect on patients' daily life. Recently, the literature has been enriched with new works that analyze possible non-pharmacological therapeutic strategies to slow cysts' enlargement and chronic kidney disease progression. Among them, dietary schemes reducing carbohydrate intake and inducing ketoses have been demonstrated to have efficacy in several pre-clinical and clinical studies. A ketogenic diet, calorie restriction, intermittent fasting, and time-restricted feeding can reduce aerobic glycolysis and inhibit the mTOR pathway, producing a reduction in cyst cell proliferation, a reduction in kidney volume, and helping to preserve kidney function. ADPKD's burden of disease has an impact on patients' quality of life, and the possibility to play sports or carry out physical exercise can help people in everyday life. The multisystemic character of the disease, especially cardiovascular involvement, needs to be carefully evaluated to establish the quality and quantity of physical activity that patients can safely carry out.

A Comparison of Urine Dilution Ability between Adult Dominant Polycystic Kidney Disease, Other Chronic Kidney Diseases, and Healthy Control Subjects: A Case-Control Study.

The final dilution of urine is regulated via aquaporin-2 water channels in the distal part of the nephron. It is unclear whether urine dilution ability in autosomal dominant polycystic kidney disease patients (ADPKD patients) differs from other patients with similar degree of impaired renal function (non-ADPKD patients). The purpose of this case control study was to measure urine dilution ability in ADPKD patients compared to non-ADPKD patients and healthy controls. Methods. Eighteen ADPKD, 16 non-ADPKD patients (both with chronic kidney disease, stage I-IV), and 18 healthy controls received an oral water load of 20 ml/kg body weight. Urine was collected in 7 consecutive periods. We measured free water clearance (CH2O), urine osmolality, urine output, fractional excretion of sodium, urine aquaporin2 (u-AQP2), and urine epithelial sodium channel (u-ENaC). Blood samples were drawn four times (at baseline, 2 h, 4 h, and 6 hours after the water load) for analyses of plasma osmolality, vasopressin, renin, angiotensin II, and aldosterone. Brachial and central blood pressure was measured regularly during the test. Results. The three groups were age and gender matched, and the patient groups had similar renal function. One hour after water load, the ADPKD patients had an increased CH2O compared to non-ADPKD patients (2.97 ± 2.42 ml/min in ADPKD patients vs. 1.31 ± 1.50 ml/min in non-ADPKD patients, p0.029). The reduction in u-AQP2 and u-ENaC occurred earlier in ADPKD than in non-ADPKD patients. Plasma concentrations of vasopressin, renin, angiotensin II, and aldosterone and blood pressure measurements did not show any differences that could explain the deviation in urine dilution capacity between the patient groups. Conclusions. ADPKD patients had a higher CH2O than non-ADPKD patients after an oral water load, and u-AQP2 and u-ENaC were more rapidly reduced than in non-ADPKD patients. Thus, urine-diluting capacity may be better preserved in ADPKD patients than in non-ADPKD patients.

Urine concentration ability is reduced to the same degree in adult dominant polycystic kidney disease compared with other chronic kidney diseases in the same CKD-stage and lower THAN in healthy control subjects - a CASE control study

BackgroundConcentration of the urine is primarily regulated via vasopressin dependent aquaporin-2 water channels in the apical membrane of kidney principal cells. It is unclear whether urine concentration ability in ADPKD differs from other patients with similar degree of impaired renal function (non-ADPKD patients). The purpose of this case control study was to measure urine concentration ability in ADPKD patients compared to non-ADPKD patients and healthy controls.MethodsA seventeen hour long water deprivation test was carried out in 17 ADPKD patients (CKD I-IV), 16 non-ADPKD patients (CKD I-IV), and 18 healthy controls. Urine was collected in 4 consecutive periods during water deprivation (12 h, 1 h, 2 h and 2 h, respectively) and analyzed for osmolality (u-Osm), output (UO), fractional excretion of sodium (FENa), aquaporin2 (u-AQP2) and ENaC (u-ENaC). Blood samples were drawn trice (after 13-, 15-, and 17 h after water deprivation) for analyses of osmolality (p-Osm), vasopressin (p-AVP), and aldosterone (p-Aldo).ResultsU-Osm was significantly lower and FENa significantly higher in both ADPKD patients and non-ADPKD patients compared to healthy controls during the last three periods of water deprivation. During the same periods, UO was higher and secretion rates of u-AQP2 and u-ENaC were lower and at the same level in the two groups of patients compared to controls. P-AVP and p-Osm did not differ significantly between the three groups. P-Aldo was higher in both groups of patients than in controls.ConclusionsUrine concentration ability was reduced to the same extent in patients with ADPKD and other chronic kidney diseases with the same level of renal function compared to healthy controls. The lower urine excretion of AQP2 and ENaC suggests that the underlying mechanism may be a reduced tubular response to vasopressin and aldosterone.Trial registrationCurrent Controlled Trial NCT04363554, date of registration: 20.08.2017.

Radiological Imaging Diagnosis of Adult Renal Cystic Diseases and Management

Background: Renal cysts are a heterogonous group of cystic renal diseases that present in approximately 40% of the patients undergoing imaging. Objective: To describe the role of the radiological imaging methods for the diagnosis of adult renal cystic diseases and their management. Methods: A descriptive study carried out for 218 patients of renal cystic diseases in adults in two Private Hospitals in Aden Province during the period from February 2006 to December 2014, diagnosed by ultrasonography, contrasted urography and computerized tomography determined the age, gender, frequency, and complications and type of treatment. Results: Autosomal dominant polycystic kidney disease (ADPKD) presented in 96 patients (44%), simple renal cysts 90 (41%), medullary sponge kidney 25 (11%), localized cystic renal disease (LCRD) six (3%) and adult multilocular cystic nephroma one (1%). Ultrasound correctly interpreted 179 patients (82%), nonvisualized 25 (11%), and inconclusive 13 (7%) contrasted urography correctly interpreted 176 (76%), nonvisualized 13 (6%) and inconclusive 19 (9%) and computerized tomography (CT) scan 199 patients (91%), six (3%) and 13 (6%) respectively. Complications occurred in 65 patients (68%) of ADPKD, 23 (25%) of simple renal cysts, 15 (60%) of medullary sponge kidney (MSK) and three patients (50%) of LCRD. Conservative treatment performed in 171 (78%) and surgical intervention in 47 patients (22%). Conclusion: The commonest renal cystic disease is adult dominant polycystic kidney. Ultrasound is inconclusive for renal cystic masses. CT scan is the effective imaging study for localized and multifocal renal cystic diseases, complications and associated pathology. The frequent complications occur in adult dominant polycystic kidney disease and medullary sponge kidney. Keywords: Adults, renal cystic diseases, imaging, management Citation: Akares SA, Bahomil AA. Radiological imaging diagnosis of adult renal cystic diseases and management. Iraqi JMS. 2020; 18(1): 12-20. doi: 10.22578/IJMS.18.1.3

Study of two pedigrees affected with adult polycystic kidney disease and male infertility resulting from novel mutations of PKD1

To explore the genetic etiology of two Chinese pedigrees affected with autosomal dominant adult polycystic kidney disease and male infertility. The coding regions of the PKD1 and PKD2 genes were subjected to PCR and Sanger sequencing. Suspected pathogenic mutations were analyzed by pedigree analysis and bioinformatics analysis. Mutation screening was performed using Sanger sequencing of blood samples obtained from 50 healthy individuals. Two novel heterozygous mutations, c.6953_6977 del(p.Arg2318Hisfs*15) and c.10937T>G (p.Val3646Gly) of the PKD1 gene were identified in the affected members of the two pedigrees, respectively, but not among to normal family members of the two pedigrees. Pedigree and bioinformatics analysis showed that both mutations were pathogenic. No pathological mutations were found in the cohort of 50 healthy individuals. Two novel mutations, c.6953_6977del(p.Arg2318Hisfs*15) and c.10937T>G (p.Val3646Gly) of the PKD1 gene may be responsible for the disease in the two pedigrees, which have enriched the spectrum of PKD1 gene mutations and provided a basis for genetic counseling and prenatal disgnosis.

A Successful Kidney Transplant for a Case of LMX1B Gene Mutation with a Positive Family History of Polycystic Kidney Disease

Nail-Patella syndrome is pleiotropic autosomal dominant disorder characterized by skeletal abnormalities and frequently renal disease. In this case report genetic analysis revealed a pathogenic heterozygous missense mutation of the LMX1B gene as c.[737G>A], p.([Arg246Gln)]. This variant is predicted to cause substitution of a basic arginine residue for a polar uncharged glutamine residue at position 246. The nucleotide at position 737 and amino acid at position 246 are both highly conserved across species. Although LMX1B mutation causing hereditary focal segmental glomerulosclerosis (FSGS) without any extra-renal involvement has been described as nail patella like renal disease (NPLRD) where there is partial impairment of transcriptional activity with these mutations leading to absence of other features of nail patella syndrome (NPS). Our case report gets interesting as patient had progressed relatively quickly to end stage renal disease. Some of heterozygous gene mutation FSGS cases are expected to recur after kidney transplantation. Our case has received a successful renal transplant from brother which is working well for the last 3 years without any evidence of recurrence. Another interesting feature of our case was the strong family history of unrelated other renal genetic disorder autosomal dominant adult polycystic kidney disease (ADPKD).

Adult Dominant Polycystic Kidney Disease (ADPKD)

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited renal cystic disease affecting up to 10% of patients requiring some form of renal replacement therapy such as hemodialysis or kidney transplant. An association between autosomal-dominant polycystic kidney disease (ADPKD) and renal cell carcinoma (RCC) has been suspected since the 1930s. Many cases of RCC in ADPKD patients have been observed and published in the meantime. The gene mutations responsible for ADPKD have been discovered in the 1990s, however a direct genetic link to RCC has not been discovered so far, and the debate about an association between these two diseases is still controversial and ongoing. Many clinical experts who have published about this issue suspect a genetic link and state that ADPKD patients are much more prone to develop RCC than patients with end-stage renal disease (ESRD) of other causes. Currently there are no clear clinical guidelines regarding early nephrectomy in ADPKD patients with growing soft tissue nodules within their native kidneys. This commentary/ review on this important clinical issue describes the experience with these patients in one institution and gives an overview of the literature.

Impact of Different Variables on Recovery Time in Patients Receiving Hemodialysis

Abstract Introduction. Patients on hemodialysis (HD) are proven to have impaired Health Related Quality of Life (HRQoL) compared to the general population. Recovery from the hemodialysis session is a permanent problem among majority of patients receiving HD treatment. A partial explanation may be the osmotic imbalance between different compartments of the body due to the fluid and electrolyte movement across the cell membrane which is a part of the HD process itself. The aim of our study was to see whether the length of recovery time (RT) is associated with different clinically relevant variables and dialysis treatment features in our HD population. Methods. We performed a cross-sectional study on patients receiving trice weekly HD in a single hemodialysis center. The recovery time was defined by posing a single question "How long does it take you to recover after a hemodialysis session?" and was calculated in hours (up to 2, 2-6, 6-12, and 12-24 hours) / minutes. Various demographic and clinical characteristics were analyzed for association with the RT. Results. The mean RT was 364.62±339.24 minutes. From all of the analyzed variables a significant statistical correlation was obtained with the level of albumin, urea, interdialytic weight gain (IDWG), protein catabolic rate (PCR), body mass index (BMI) and the level of hemoglobin (p<0.05 for all parameters). The longest mean RT had patients with hypertension and glomerulonephritis as a primary cause of ESRD and the shortest, patients with an adult dominant polycystic kidney disease. With the multiple regression analysis a significant correlation was obtained only for the level of hemoglobin (Hb) with a coefficient for partial regression analysis - 0.2635. The t-test showed that the influence of the level of hemoglobin on recovery time in patients was statistically significant (p = 0.039). Conclusions. RT in our study was associated with IDWG, albumin, urea, BMI, and PCR, while the level of hemoglobin was also shown to have a significant impact on the RT and on patients’ overall health status. Hence, we could conclude that maintaining Hb levels in dialysis patients within reference values among the other benefits, may improve the recovery time and HRQoL of our patients.

Autopsy report with clinical and pathophysiologic discussion of autosomal dominant adult polycystic kidney disease.

The average weight of a kidney is approximately 135 gm, measuring on average 10 × 6 × 4 cm. In hereditary conditions, autosomal dominant and autosomal recessive polycystic kidney disease, the shape, size, and the weight can be significantly abnormal, causing progressive renal failure, often necessitating dialysis or renal transplant for survival. We report a case of adult polycystic kidney disease in a 50-year-old female without a family history, who died of complications of the disease which included accelerated hypertension, and renal and cardiac failure.

The Biobank of Nephrological Diseases in the Netherlands cohort: the String of Pearls Initiative collaboration on chronic kidney disease in the university medical centers in the Netherlands

Despite advances in preventive therapy, prognosis in chronic kidney disease (CKD) is still grim. Clinical cohorts of CKD patients provide a strategic resource to identify factors that drive progression in the context of clinical care and to provide a basis for improvement of outcome. The combination with biobanking, moreover, provides a resource for fundamental and translational studies. In 2007, the Dutch government initiated and funded the String of Pearls Initiative (PSI), a strategic effort to establish infrastructure for disease-based biobanking in the University Medical Centres (UMCs) in the Netherlands, in a 4-year start-up period. CKD was among the conditions selected for biobanking, and this resulted in the establishment of the Biobank of Nephrological Diseases-NL (BIND-NL) cohort. Patients with CKD Stages 1-4 are eligible. The data architecture is designed to reflect routine care, with specific issues added for enrichment, e.g. questionnaires. Thus, the collected clinical and biochemical data are those required by prevailing guidelines for routine nephrology care, with a minimal dataset for all patients, and diagnosis-specific data for the diagnostic categories of primary and secondary glomerular disorders and adult dominant polycystic kidney disease, respectively. The dataset is supplemented by a biobank, containing serum, plasma, urine and DNA. The cohort will be longitudinally monitored, with yearly follow-up for clinical outcome. Future linking of the data to those from the national registries for renal replacement therapy is foreseen to follow the patients' lifeline throughout the different phases of renal disease and different treatment modalities. In the design of the data architecture, care was taken to ensure future exchangeability of data with other CKD cohorts by applying the data harmonization format of the Renal DataSHaPER, with a dataset based upon standardized indicator sets to facilitate collaboration with other CKD cohorts. Enrolment started in 2010, and over 2200 eligible patients have been enrolled in the different UMCs. Follow-up of enrolled patients has started, and enrolment will continue at a slower rate. The aggregation and standardization of clinical data and biosamples from large numbers of CKD patients will be a strategic resource not only for clinical and translational research, but also by its basis in routine clinical care for clinical governance and quality improvement projects.

Long-Term Impact of Laparoscopic Cyst Decortication on Renal Function, Hypertension and Pain Control in Patients with Autosomal Dominant Polycystic Kidney Disease

Cyst proliferation in patients with autosomal dominant polycystic kidney disease is associated with renal failure, hypertension and pain. We examined the long-term impact of laparoscopic cyst decortication on renal function, hypertension and pain control in patients with adult dominant polycystic kidney disease presenting with refractory pain. Between 1994 and 2003, 37 patients with adult dominant polycystic kidney disease underwent laparoscopic cyst decortication at Barnes-Jewish Hospital. A total of 19 patients (4 male, 15 female) with at least 3-year followup were included in the study. Renal function was evaluated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) estimated glomerular filtration rate formula. End stage renal disease was defined as progression to transplant, dialysis or stage 5 chronic kidney disease. Hypertension was evaluated using the antihypertensive therapeutic index. Pain assessment was based primarily on a telephone questionnaire. At a mean followup of 10.9 years (range 6.4 to 16.9), 67% of evaluable patients reported more than 50% improvement in pain. Ten patients had progression to end stage renal disease--3 dialysis, 6 transplant, and 1 chronic kidney disease stage 5. Two patients had stage 5 chronic kidney disease at initial presentation. A comparison of preoperative estimated glomerular filtration rate between patients with and those without end stage renal disease revealed a lower preoperative estimated glomerular filtration rate in the former group (43.4 vs 75.4 ml/minute/1.73 m(2), p = 0.01). Of the patients 53% had an improved or stable antihypertensive therapeutic index at last followup, although no improvement in mean overall antihypertensive therapeutic index was noted (4.7 pre-laparoscopic cyst decortications vs 7.0 post-laparoscopic cyst decortications, p = 0.28). Durable pain relief but not hypertension control was seen at 10-year followup. Preoperative estimated glomerular filtration rate is a strong predictor of post-laparoscopic cyst decortication progression to end stage renal disease. A cautious approach with laparoscopic cyst decortication should be taken in patients with poor preoperative renal function.

Recent advances in studies on autosomal dominant adult polycystic kidney disease

Adult polycystic kidney disease (APKD) is a severe autosomal dominant inheritable renal disease with high incidence. Because of the late-onset of the disease, patients might have transferred the disease gene to the next generation when diagnosis is made. Since its pathogenic molecular mechanism is still not completely clear and the shortage of effective medicines, the prevention and treatment of the disease is still not satisfactory. In the present article, the recent advances in the research on the pathogenesis, gene diagnosis and management of APKD are reviewed.

ERK1/2-Dependent Vascular Endothelial Growth Factor Signaling Sustains Cyst Growth in Polycystin-2 Defective Mice

Severe polycystic liver disease can complicate adult dominant polycystic kidney disease, a genetic disease caused by defects in polycystin-1 (Pkd1) or polycystin-2 (Pkd2). Liver cyst epithelial cells (LCECs) express vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2. We investigated the effects of VEGF on liver cyst growth and autocrine VEGF signaling in mice with Pkd1 and Pkd2 conditional knockouts. We studied mice in which Pkd1 or Pkd2 were conditionally inactivated following exposure to tamoxifen; these mice were called Pkd1(flox/-):pCxCreER (Pkd1KO) and Pkd2(flox/-):pCxCreER (Pkd2KO). Pkd1KO and Pkd2KO mice developed liver defects; their LCECs expressed VEGF, VEGFR-2, hypoxia-inducible factor (HIF)-1alpha, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), and proliferating cell nuclear antigen (PCNA). In Pkd2KO but not Pkd1KO mice, exposure to the VEGFR-2 inhibitor SU5416 significantly reduced liver cyst development, liver/body weight ratio, and expression of pERK and PCNA. VEGF secretion and phosphorylation of ERK1/2 and VEGFR-2 were significantly increased in cultured LCECs from Pkd2KO compared with Pkd1KO mice. Inhibition of protein kinase A (PKA) reduced VEGF secretion and pERK1/2 expression. Addition of VEGF to LCECs from Pkd2KO mice increased phosphorylated VEGFR-2 and phosphorylated mitogen signal-regulated kinase (MEK) expression and induced phosphorylation of ERK1/2; this was inhibited by SU5416. Expression of HIF-1alpha increased in parallel with secretion of VEGF following LCEC stimulation. VEGF-induced cell proliferation was inhibited by the MEK inhibitor U1026 and by ERK1/2 small interfering RNA. The PKA-ERK1/2-VEGF signaling pathway promotes growth of liver cysts in mice. In Pkd2-defective LCECs, PKA-dependent ERK1/2 signaling controls HIF-1alpha-dependent VEGF secretion and VEGFR-2 signaling. Autocrine and paracrine VEGF signaling promotes the growth of liver cysts in Pkd2KO mice. VEGF inhibitors might be used to treat patients with polycystic liver disease.

Male infertility associated with adult dominant polycystic kidney disease: a case series

Although described earlier, the association of male infertility with adult dominant polycystic kidney disease (ADPKD) is quite rare and unfamiliar to some of the multidisciplinary team members caring for affected men. Infertile men diagnosed to have ADPKD were evaluated by clinical characteristics including testis volume, as well as serum hormone levels, semen analysis, and transrectal ultrasonography (TRUS) because of low volume ejaculate. Semen analysis revealed low-normal volume, normal pH, and azoospermia/virtual azoospermia. Serum hormones were within the normal range. Transrectal ultrasonography demonstrated cystic dilatation of the seminal vesicles in all three men. Patients should be referred for andrological evaluation of a presentation similar to obstructive azoospermia. Their potential to achieve paternity by surgical sperm retrieval combined with assisted reproductive technology is another example of cooperation between andrologists and gynecologists.

Renal replacement therapy in adult dominant polycystic kidney disease - multicentre study

Adult polycystic kidney disease (APKD) is the most common hereditary kidney disease in humans. The course of the disease is accompanied by numerous complications. OBJECTIVE The aim was to assess the prevalence, clinical course and outcome of adult dominant polycystic kidney disease (ADPKD) patients on renal replacement therapy. Medical data on 700 haemodialyzed (HD) and 500 transplanted patients treated in 10 Serbian centres from 1996 to 2000 were retrospectively analyzed. While ADPKD patients accounted for 13% of HD patients in Serbia in 2000, in the period between 1996 and 2000, the percent of patients with ADPKD in the population of patients starting HD in 8 examined centres changed from 13.5% to 6.9%. The total number of 180 ADPKD patients on HD was analyzed (96 males; aged 55 years at HD onset). Their HD lasted between 1 and 22 years: males started HD 1.3 years earlier and spent on HD 1.1 years less than females. In 53% of HD patients one or more family members had ADPKD but the cause of death was unknown for many family members. Hypertension was present in 75% of ADPKD patients, anaemia in 37% and other organ involvement (usually liver) was found in 53 patients. Fifty patients experienced AV fistula thrombosis and a vascular prosthesis had to be used in 9 of them. A hundred and two HD patients died (aged between 38 and 78 years, on HD for 5.3 years). The causes of death were stroke (19.6%), cardiovascular diseases (29%), infections, while 5% of patients died with the picture of acute abdomen. Among 500 transplanted patients, there were 20 patients with ADPKD (11 males, ages between 35 and 56 years at the time of transplantation) and 14 of them received graft from cadaver donor. Uni- or bilateral nephrectomy was done in 4 patients in the pretransplant preparation, and in another two early after transplantation due to urinary infection. Three patients restarted HD in the first 3 months after transplantation due to acute tubular necrosis and 10 patients died 56.5 months after the transplantation. The known causes of death were cardiovascular disease (3 patients), severe gastrointestinal bleeding (2 patients), infection (2 patients) and cancer (2 patients). The obtained results showed that it was possible to provide a favourable outcome of patients with APBB on renal replacement therapy in spite of numerous complications.

A case of primary cutaneous aspergillosis in a renal transplant recipient

Opportunistic fungal infections are life-threatening complications which are a major cause of morbidity and mortality in immunocompromized hosts such as those who have undergone organ transplantation. Aspergillosis comprises a spectrum of disease caused by a ubiquitous saprophytic mold. Invasive aspergillus is a serious life-threatening complication in immunocompromised hosts. Primary cutaneous aspergillosis occurs relatively less frequently and is poorly characterized. We report a case of cutaneous aspergillosis in a 51-year-old renal transplant recipient, which was successfully treated with local excision and concomitant antifungal therapy. Case A 51-year-old male renal transplant recipient presented with cutaneous nodules on the dorsum of the right hand. He underwent renal transplantation for end-stage renal disease due to adult dominant polycystic kidney disease (ADPKD) 3 years prior. Initially he suffered an acute rejection episode that was treated with steroid pulse and OKT3 therapy. Eventually he was stabilized on a combination of tacrolimus, prednisone, and mycophenolate mofetil. Three years after transplanation, he developed painless multiple (largest one 5 × 3 cm sized) nodules on the dorsum of his right hand. He was afebrile with no systemic symptoms. A skin biopsy showed a dense solid infiltration of giant cells, histiocytes, and lymphoplasma cells admixed with intra- and extracelluar fungal hyphae and spores. The hyphae were septate and acute angle branching, which was consistent with aspergillosis. Oral itraconazole 200 mg/d for 5 weeks was ineffective. Treatment with liposomal amphotericin B for 4 weeks was initated and MMF was discontinued. The medication was well tolerated with no hepatotoxic effects. Although new lesions did not appear, existing ones did not significantly improve after 4 weeks of treatment. Therefore, most lesions were excised surgically and liposomal amphotericin B continued for 2 weeks followed by treatment with oral fluconazole for 2 months. Ten moths later there was no evidence of recurrence.

Screening for aneurysms in risk groups: meaningful?

There is a controversy discussion on screening for aneurysms in risk groups. True guidelines do not exist so far. It seems that screening for familial aneurysms is not advisable today. But adult dominant polycystic kidney disease (ADPKD) patients with a familial history of SAH should be screened because of a high prevalence rate of 25% for intracranial aneurysms in this population. Screening should be performed every 2 to 3 years by MRI angiography in this special risk group.

Tuberous Sclerosis Complex with an Unruptured Intracranial Aneurysm: Manifestations of Contiguous Gene Syndrome

With the advancement of molecular genetics, the deletion of the TSC2/PKD1 gene at chromosome 16p13.3 has been discovered to be responsible for the tuberous sclerosis complex sharing some of the clinical manifestations of autosomal dominant adult polycystic kidney disease such as multiple renal cysts and intracranial aneurysms. The unruptured aneurysm in tuberous sclerosis complex is far beyond the meaning it has in general population. The risk of aneurysmal hemorrhage in tuberous sclerosis complex may be higher than that in autosomal dominant adult polycystic kidney disease due to the synergistic effect of gene deletion and certainly much higher than that in the general population. For such high-risk patients with intracranial aneurysms doomed to subarachnoid hemorrh age, magnetic resonance angiography plays an important role in screening and follow-up, especially more critically for patients with contiguous gene syndrome. Endovascular coil embolization should be the first choice of treatment for un ruptured intracranial aneurysms.

The vasculopathy of autosomal dominant polycystic kidney disease: Insights from animal models

A 37-year-old white man with autosomal dominant polycystic kidney disease (ADPKD) was admitted to Boston's Beth Israel Hospital with sudden severe headache of two-hour duration. He was unconscious on admission. Emergency angiography revealed a ruptured 15 mm cerebral aneurysm. Emergency surgery to clip the aneurysm was unsuccessful, and the patient died 36 hours after admission. His serum creatinine was 3.2 mg/dL on admission; the rest of his laboratory values were within normal limits. A request for an autopsy was denied. At age 20, the patient and his then 15-year-old sister had abdominal ultrasound examinations that revealed bilateral renal cysts, consistent with the diagnosis of ADPKD. At age 32, the patient had a sudden, relatively severe, acute myocardial infarction (MI). Cardiac catheterization revealed three-vessel disease, and he subsequently underwent a triple coronary artery bypass operation. Throughout his medical course, the patient's blood pressure was in the 120/80 to 140/80 mm Hg range while he was taking lisinopril, 10 mg/day, which was started after his MI. The patient's mother has ADPKD and end-stage renal disease, and she is on hemodialysis. She recently underwent unsuccessful renal transplantation. There is no known family history of cerebral aneurysms. However, the mother had two cerebrovascular accidents and recovered from both. The patient's father had an MI at age 32, but he lived to age 64. A paternal uncle also died at an early age of an MI. The patient's younger sister was later screened for cerebral aneurysms and the test was negative. The patient's two young children have not been screened for ADPKD.