Family History Of Autosomal Dominant Polycystic Kidney Disease Research Articles

Long-Term Effects of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: Predictors of Treatment Response and Safety over 6 Years of Continuous Therapy.

Tolvaptan, an oral vasopressin V2 receptor antagonist, reduces renal volume expansion and loss of renal function in patients with autosomal dominant polycystic kidney disease (ADPKD). Data for predictive factors indicating patients more likely to benefit from long-term tolvaptan are lacking. Data were retrospectively collected from 55 patients on tolvaptan for 6 years. Changes in renal function, progression of renal dysfunction (estimated glomerular filtration rate [eGFR], 1-year change in eGFR [ΔeGFR/year]), and renal volume (total kidney volume [TKV], percentage 1-year change in TKV [ΔTKV%/year]) were evaluated at 3-years pre-tolvaptan, at baseline, and at 6 years. In 76.4% of patients, ΔeGFR/year improved at 6 years. The average 6-year ΔeGFR/year (range) minus baseline ΔeGFR/year: 3.024 (-8.77-20.58 mL/min/1.73 m2). The increase in TKV was reduced for the first 3 years. A higher BMI was associated with less of an improvement in ΔeGFR (p = 0.027), and family history was associated with more of an improvement in ΔeGFR (p = 0.044). Hypernatremia was generally mild; 3 patients had moderate-to-severe hyponatremia due to prolonged, excessive water intake in response to water diuresis-a side effect of tolvaptan. Family history of ADPKD and baseline BMI were contributing factors for ΔeGFR/year improvement on tolvaptan. Hyponatremia should be monitored with long-term tolvaptan administration.

Dapagliflozin administration for 1year promoted kidney enlargement in patient with ADPKD.

To date, there is insufficient evidence regarding use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with autosomal-dominant polycystic kidney disease (ADPKD), as such cases have been excluded from previous clinical trials exploring the kidney protection effects of such medications. Here, findings of an ADPKD patient who received dapagliflozin, a selective SGLT2 inhibitor, for 1year are presented. A 38-year-old woman with a family history of ADPKD wished for treatment with dapagliflozin. After starting administration at 10mg/day, total kidney volume (TKV) continued to increase, from 1641 to 1764mL after 84days and then to 2297mL after 340days. The estimated glomerular filtration rate (eGFR) was also decreased from 67.3 to 56.2mL/min/1.73m2, and then to 51.4mL/min/1.73m2 at those times. Immediately after discontinuation of dapagliflozin, TKV and eGFR were slightly improved to 2263mL and 55.1mL/min/1.73m2, respectively. Following a review of basic research studies, we consider that increased intratubular urinary osmotic pressure, compensatory glucose reabsorption by sodium-glucose cotransporter-1 in the late proximal tubule, and hypertrophy shown in collected cells caused by increased vasopressin may be associated with ADPKD disease progression. Caution may be needed when administering dapagliflozin to patients with ADPKD.

Atypical Polycystic Kidney Disease as defined by Imaging

Using age- and height-adjusted total kidney volume, the Mayo Clinic Imaging Classification provides a validated approach to assess the risk of chronic kidney disease (CKD) progression in autosomal dominant polycystic kidney disease (ADPKD), but requires excluding patients with atypical imaging patterns, whose clinical characteristics have been poorly defined. We report an analysis of the prevalence, clinical and genetic characteristics of patients with atypical polycystic kidney disease by imaging. Patients from the extended Toronto Genetic Epidemiology Study of Polycystic Kidney Disease recruited between 2016 and 2018 completed a standardized clinical questionnaire, kidney function assessment, genetic testing, and kidney imaging by magnetic resonance or computed tomography. We compared the prevalence, clinical features, genetics, and renal prognosis of atypical versus typical polycystic kidney disease by imaging. Forty-six of the 523 (8.8%) patients displayed atypical polycystic kidney disease by imaging; they were older (55 vs. 43 years; P < 0.001), and less likely to have a family history of ADPKD (26.1% vs. 74.6%; P < 0.001), a detectable PKD1 or PKD2 mutation (9.2% vs. 80.4%; P < 0.001), or progression to CKD stage 3 or stage 5 (P < 0.001). Patients with atypical polycystic kidney disease by imaging represent a distinct prognostic group with a low likelihood of progression to CKD.

MO008: Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) without a Clear Family History have Rapid Progression and Poor Prognosis

Abstract BACKGROUND AND AIMS A small percentage of patients with autosomal dominant polycystic kidney disease (ADPKD) have no clear family history. The clinical course and prognosis of the disease in this subgroup of patients may be different. The present study investigates the progression and prognostication of end-stage renal disease (ESRD) in a large cohort of patients with and without a family history of ADPKD. METHOD This study enrolled 291 patients who were being followed in a specialized outpatient ADPKD clinic. Patients having a total of more than 10 kidney cysts in a recent magnetic resonance imaging (MRI) scan were included in the study even if they had no clear family history or confirmatory genetic test. At enrollment, total kidney volume was calculated by MRI, and the Mayo Clinic Imagining Category (MCIC) was determined. The prediction of ESRD (future estimated-glomerular filtration rate [e-GFR &amp;lt; 10 mL/min] based on the Mayo Clinic formula (which takes into consideration age, TKV, e-GFR, gender, race and MCIC) was also calculated. Demographics, medical and laboratory data were recorded using a standardized form. T-test, x2 and Mann–Whitney test were used for statistical analysis. RESULTS Of the 291 patients included in the study, 34 (11.68%) had no clear family history of ADPKD, and 257 (88.32%) had a clear family history. Age, gender, presence or not, and age at diagnosis of hypertension as well as BMI were similar in the two groups (P = 0.369, 0.398, 0.170, 0.295, 0.597, respectively). The age at diagnosis of ADPKD was similar between patients with and without a clear family history (P = 0.125) as well as, the e-GFR, the stage of chronic kidney disease and albuminuria (P = NS). The TKV tended to be higher in patients without a clear family history (median, [range]), 2210.3 (440.7–9137.5) mL versus 1649.9 (215.7–10 425.9) mL in those with a family history of ADPKD (P = 0.09), and the same was valid for the height-adjusted TKV (P = 0.08). In MCIC 1C, 1D and 1E, more patients without a known family history of ADPKD were classified than patients with a family history of ADPKD (88.89% versus 70.14%), and vice versa in MCIC 1A and 1B (11.11% versus 29.86%; P = 0.04). Finally, the ESRD prediction was (median, [range]) 15.66 (1–42) years for the patients without a clear family history and 34.1 (1–346) years for those with a clear family history of ADPKD (P = 0.025). CONCLUSION Patients with ADPKD without a clear family history tend to have a more rapid progression and a worse renal prognosis than those with a clear family history of the same disease.

POS-240 RENAL SIZE IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by progressive enlargement of kidney cysts and size leading to chronic Kidney Disease (CKD) .The decrease in kidney function is strongly correlated with the severity and growth of kidney cysts. We aimed to describe kidney size in patients with ADPKD. This is a retrospective descriptive study. A total of 80 patients with ADPKD followed up at the nephrology department of Sahloul University Hospital during the period 2006 _2019 were included in our analysis. Kidney size and cysts number were measured using Ultrasound (US). The mean age of the study patients was 55, 8 ± 14, 2 years. There were 42 female and 38 male patients (sex ratio: male/female = 0, 9). A family history of ADPKD was found in 78, 8% of cases. Thirty five patients had CKD stage 1, 11 had CKD stage 2, 11 had CKD stage 3, 9 had CKD stage 4 and 14 had CKD stage 5. The average value of right kidney size was 15,2cm with maximum size going to 27cm.The average value of left kidney size was 15,7cm with maximum size going to 25cm. Twenty eight percent of patients with CKD stage 4 and stage 5 had kidney size ≥16,5cm.For kidney cysts number: Tabled 1Cysts numberFrequency4-614 patients (17, 5%)6-1032 patients (40%)More than 1016 patients (20%) Open table in a new tab Our study confirms that ADPKD is characterized by the almost constant increase in the size of the kidneys.

Clinical practice guideline monitoring children and young people with, or at risk of developing autosomal dominant polycystic kidney disease (ADPKD)

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is thought to affect about 1 in 1000 people in the UK. ADPKD causes a progressive decline in kidney function, with kidney failure tending to occur in middle age. Children and young people with ADPKD may not have any symptoms. However they may have high blood pressure, which may accelerate progression to later stages of chronic kidney disease.There is uncertainty and variation in how health professionals manage children and young people with confirmed or a family history of ADPKD, because of a lack of evidence. For example, health professionals may be unsure about when to test children’s blood pressure and how often to monitor it in the hospital clinic or at the GP. They may have different approaches in recommending scanning or genetic testing for ADPKD in childhood, with some recommending waiting until the young person is mature enough to make this decision his or herself.This guideline is intended to help families affected by ADPKD by making sure that:health professionals with specialist knowledge in ADPKD offer you information on inheritance and potential benefits and harms of testing for ADPKD.the decision to test and the method of testing for ADPKD in children and young people is shared between you or your family and the health professionalsblood pressure assessment is undertaken regularly in children and young people at risk of developing ADPKD

Clinical study on autosomal dominant polycystic kidney disease among North Tunisians

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, which usually manifests in adulthood. It is characterized by the development of multiple cysts in the kidneys and many other extrarenal manifestations. We aimed to determine the factors that contribute to the progression of ADPKD to end-stage renal disease (ESRD). In a retrospective multicentric study, we reviewed the records of 569 patients with ADPKD, hospitalized at a nephrology department or followed up at the outpatient department of university and regional hospitals, covering the north and center of the country, during the period 1969-2016. The mean age of the study patients was 48.54 ± 13.68 years and 14% were young adults (<40 years). There were 272 female and 297 male patients (sex ratio: male/female = 1.09). A family history of ADPKD was found in 43.7% of cases. Renal symptoms were dominated by loin pain, renal failure, hypertension, and hematuria, seen in, respectively, 51.9%, 48.2%, 29.1%, and 24.6% of the patients. The median serum creatinine level was 459 μmol/L (range: 47-2454), and hypertension had preceded the onset of ADPKD in 28.8% of cases. Extrarenal manifestations consisted of urologic complications (54.6%), liver cysts (43.5%), cardiac involvement (31.9%), cerebral aneurysms (12.9%), and gastrointestinal involvement (9.4%). ESRD occurred in 43.1% after a mean follow-up of 47 months (range: 0-384). Risk factors for poor renal prognosis were age >40 years (P = 0.009), hematuria (P = 0.034), hemoglobin >14 g/dL (P = 0.0013), high uric acid level (P = 0.001), and leukocyturia (P = 0.02). Death occurred in 59 cases (10.3%), mostly caused by infections (44.1%). In our study, ADPKD was lately diagnosed in most cases. Family screening is important, which will enable early detection and management of the complications associated with ADPKD.

Hereditary Kidney Disease: All Family Members Are Affected.

In families with hereditary kidney disease, it is common to refer to “affected” and “unaffected” family members, but in reality, all family members are affected. All face uncertainty about whether they have the disease or can pass it on, and whether to be tested. Those with the disease face

Clinical presentation and outcome of autosomal dominant polycystic kidney disease in Nigeria.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is presumably rare in Africa. Knowledge about the disease in Nigeria is limited as demonstrated by scanty articles on the subject. To determine the pattern of clinical presentation and outcome of ADPKD among ADPKD patients. ADPKD subjects were prospectively studied between January 1996 and December 2010. Their demographics, clinical and investigation parameters were documented. Dependency on dialysis, renal transplant and death were the final outcomes. Forty one patients (M:F=1.3:1) with mean age of 48.6±4.6 years were studied. ADPKD was diagnosed at 2.73 cases per annum. Family history of ADPKD and hypertension were present in 56.1% and 82.9% respectively. Their mean systolic and diastolic blood pressures were 166.9 ±23.6 and 104 ±21.2 respectively.Nocturia (78.0%) and loin pain (68.3%) were the most common presenting symptoms. Liver cysts (31.7%) and aortic regurgitation (22.0%) were the predominant extra-renal manifestations.Twenty three (56.1%) received haemodialysis; no renal transplantation. Death rate was 51.2%. Presence of uraemia and intra-cerebral aneurysm contributed significantly to mortality. ADPKD may not be so rare in Nigeria. Awareness campaign to change attitude of family members to screening and further studies using newer criteria for diagnosis of ADPKD should be conducted.

Clinical manifestations, imaging findings and laboratory abnormalities in 51 patients with autosomal dominant polycystic kidney disease: Experience at Tirupati, South India

Background: Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of renal failure. Sparse recent data are available on clinical presentation ADPKD from India. Methods: We retrospectively studied the clinical presentation, imaging findings and laboratory abnormalities in 51 patients diagnosed to have ADPKD at our tertiary care teaching hospital at Tirupati, South India. Results: Their mean age at presentation was 49.1± 13.2 years; there were 32 (63%) males. Salient renal clinical manifestations at initial presentation included abdominal pain (47%); fever (35%), shortness of breath (33%); palpable mass per abdomen (25%); burning micturition (20%); haematuria (10%); and renal/ureteric caliculi (12%). Other manifestations were headache (21%); altered sensorium (12%); intracerebral bleed (8%) and chest pain (8%). Family history of ADPKD was present in 13 (26%) patients. On imaging studies kidneys were normal sized in 39%, enlarged in 59% and small sized in one patient; co-existent liver cysts were found in 12 patients. Hypertension (n = 20, 40%); chronic kidney disease (CKD) (n = 36, 71%) were evident at initial presentation. Other associated co-morbid conditions were type 2 diabetes mellitus (n = 6); Marfan's syndrome with mitral valve prolapsed and renal cell carcinoma (one patient each). Conclusions: In Tirupati, South India, ADPKD most commonly presented in fourth or fifth decade of life. Males were affected more frequently than females. Presence of CKD, hypertension at the time of inital diagnosis suggests that ADPKD is diagnosed late in the course of the disease. A high index of suspicion, specific diagnostic work-up including abdominal ultrasonography is required to diagnose ADPKD.

Sonographic analysis of adult polycystic kidney disease: Retrospective data from South-East Nigeria

Autosomal dominant polycystic kidney disease (APKD), an inheritable multisystem disease characterized by intrarenal and at times extrarenal disease, has been studied extensively among Caucasian populations. Despite the fact that being black is a risk factor for progressive disease, there is paucity of local published data. As a result, true local incidence and peculiarities in clinical and sonographic characteristics are unknown. To present data from 19 patients diagnosed with APKD in a medium-sized facility over a 16-year period. A retrospective search was done on the ultrasound registers for patients who had undergone abdominal ultrasound in 16 years (1997-2013). Of the 29 sonographic diagnoses of bilateral PKD made, only 19 had complete records and were included in the study. Data extracted were- age, sex, working diagnosis, renal size, diameter of renal cysts, presence or absence of extrarenal cysts, family history of renal cystic disease, blood pressure at diagnosis, and patient outcome. A total of 19 diagnoses of APKD were made- 12 males and seven females with a sex ratio of 1:0.6. Total mean age was 54.8 years (range 31-79 years)- 40.1 years for females and 57.2 years for males. In 89.5% of cases, no family history of APKD was obtained. Only six (31.6%) patients were hypertensive at presentation and three patients (16%) were already in renal failure. Ultrasound showed a mean renal size of 88.92 cm² for the right kidney and 98.97 cm² for the left. Mean cyst diameter was 3.46 cm (range 2.08-4.85 cm). Only one patient had documented extrarenal cystic disease. Two patients were lost to renal failure and congestive cardiac failure. APKD appears to be uncommon in our environment; however, more studies may be elucidatory. Standard sonographic protocol for collecting data from patients with APKD is needed.

Prevalence of Cardiovascular Events in Patients with Autosomal Dominant Polycystic Kidney Disease

Background: This study evaluates the prevalence of cardiovascular events in autosomal dominant polycystic kidney disease (ADPKD) patients. Methods: We distributed surveys to 1,439 subjects from our ADPKD research database. In total, 426 subjects completed and returned surveys; 7 of these were from children and were excluded from the study. Results: The patients who responded were female (63.2%), nonHispanic (88.1%) and white (93.6%). The mean age of the total group was 53.2 ± 13.7 years; 82.8% had a family history of ADPKD and 32.5% had reached end-stage renal disease (ESRD). With respect to cardiovascular risk factors, 86.6% were hypertensive with a mean age at diagnosis of 36.9 ± 12.9 years and hypertension was significantly more prevalent in males. In addition, 19.6% of the subjects were obese, 20.8% were smokers, 8.7% had diabetes, 45.7% had high cholesterol and 17.8% were sedentary. The most prevalent self-reported cardiovascular events were arrhythmias (25.9%), evidence of peripheral vascular disease (16.5%), heart valve problems (14.4%), cardiac enlargement (9.5%), stroke or cerebral bleeding (7.5%), myocardial infarction (6%) and brain aneurysm (5.0%). The most commonly used antihypertensive medications were renin-angiotensin inhibitors used by 75% of ADPKD patients. Older ADPKD patients and those at ESRD had a significantly higher incidence of cardiovascular events. Conclusion: These findings support the high prevalence of cardiovascular risk factors and events in ADPKD patients which contribute to a greater mortality risk. Due to the prevalence of cardiovascular risk factors in the ADPKD population, early diagnosis and clinical intervention are recommended.

A Prospective Study on Clinical Profile of Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Jammu for a Period of 1 Year

The Present Study was conducted in department of Medicine, Govt. Medical College, jammu, Where a total of 41 patients—29 males and 12 females—fulfilled the inclusion criteria of ADPKD, were gathered during the period of 1 year starting from Nov. 2011 to Oct. 2012. All the patients were subjected to a detailed history, clinical examination and laboratory investigations. X-ray chest (PA view), ECG and ultrasound of abdomen for kidneys, liver and spleen were done. Intravenous pyelogram and CT scan of abdomen was done when a definitive diagnosis of (ADPKD) could not be made on abdominal ultrasound. Echocardiography was done to evaluate cardiac murmurs and associated mitral valve prolapse, based on standard criteria. Male to female patients with ADPKD was 2.42:1. Maximum 17 (41.5%) patients of both gender were seen in 30 - 40 years age group, Family history of ADPKD was present in 18 (43.9%) patients; Hypertension, alone or in combination with renal failure, was present in 65.8% patients; Hypertension alone was present in 19 (46.3%) patients;8 (19.5%) patients with hypertension had renal failure; Low back pain was present in 24 (58.5%) and abdominal pain in 22 (53.7%) patients; 15 (36.6%) patients presented with at least one episode of gross haematuria; Headache was experienced by 18 (43.9%) patients. On clinical examination, 24 (58.5%) were found to have palpable kidney and 10 (24.4%) had palpable liver. Spleen was palpable in 1 (2.4%) patient, Murmur of mitral valve prolapse was found in 2 (4.9%) Patients; 3 (7.3%) patients having left ventricular hypertrophy; mean Hb was 11.2 g/dL. The liver cysts were found in 24.4% of the patients; Out of 10 (24.4%) patients with hepatic cyst involvement, 1 patient each was found to have evidence of portal hypertension and evidence of hepatic cyst infection. In the present study, hypertension was most common presentation of this disease. So, control of hypertension is very important to prevent progression of this disease. Patients who are detected to have ADPKD should be regularly followed-up to prevent further progression by timely intervention. Also, family members of patients should be screened for disease and initiate treatment as early as possible.

Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients

Total kidney and cyst volumes have been used to quantify disease progression in autosomal dominant polycystic kidney disease (ADPKD), but a causal relationship with progression to renal failure has not been demonstrated. Advanced image processing recently allowed to quantify extracystic tissue, and to identify an additional tissue component named "intermediate," appearing hypoenhanced on contrast-enhanced computed tomography (CT). The aim of this study is to provide a histological characterization of intermediate volume, investigate its relation with renal function, and provide preliminary evidence of its role in long-term prediction of functional loss. Three ADPKD patients underwent contrast-enhanced CT scans before nephrectomy. Histological samples of intermediate volume were drawn from the excised kidneys, and stained with hematoxylin and eosin and with saturated picrosirius solution for histological analysis. Intermediate volume showed major structural changes, characterized by tubular dilation and atrophy, microcysts, inflammatory cell infiltrate, vascular sclerosis, and extended peritubular interstitial fibrosis. A significant correlation (r = -0.69, P < 0.001) between relative intermediate volume and baseline renal function was found in 21 ADPKD patients. Long-term prediction of renal functional loss was investigated in an independent cohort of 13 ADPKD patients, followed for 3 to 8 years. Intermediate volume, but not total kidney or cyst volume, significantly correlated with glomerular filtration rate decline (r = -0.79, P < 0.005). These findings suggest that intermediate volume may represent a suitable surrogate marker of ADPKD progression and a novel therapeutic target.

Aberrant PKD2 splicing due to a presumed novel missense mutation in autosomal-dominant polycystic kidney disease

Autosomal-dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder characterized by abnormal proliferation of renal tubular epithelium, leading to massive kidney enlargement and progressive chronic kidney disease. ADPKD is caused by mutations in PKD1 and PKD2 genes. Herein, we describe and characterize a novel missense mutation in the PKD2 gene (c.1320G>T) in a 41-year-old White man with kidney cysts and a family history of ADPKD. This mutation abolishes a conserved acceptor splice site of intron 5, resulting in a premature termination following the addition of three aberrant amino acids (PKD2 p.L441C fsX4). We demonstrate that the aberrantly spliced transcript is found in substantial amounts in the patient's peripheral blood leukocytes (PBL), and show that this alternative splicing of exon 6 occurs, to a lesser magnitude, in other patients with ADPKD and in normal control individuals. The biological and clinical significance of this splice variant in ADPKD is currently unknown.

Renal Ultrasonographic Evaluation in Children at Risk of Autosomal Dominant Polycystic Kidney Disease

To date, there are no criteria for diagnosing autosomal dominant polycystic kidney disease (ADPKD) in at-risk children 15 years or younger. Longitudinal (retrospective cohort study). 420 children (mean age, 8.3 +/- 4.2 years) with a family history of ADPKD were studied. Renal ultrasonography was performed for cyst detection. Urine protein was measured using two 24-hour urine collections. Glomerular filtration rate was calculated using the Schwartz formula. Blood pressure measurements were performed in the arm with the highest blood pressure, using an appropriate cuff size. Standard 2-dimensional and Doppler echocardiography was performed for measuring left ventricular mass index. None. Presence of renal cysts. Renal cysts were detected in 193 children and no cysts were detected in 227 children. In children with renal cysts, 150 had bilateral and 43 had unilateral cysts. Children with bilateral cysts had larger kidneys and more hypertension than children with unilateral or no cysts. Follow-up in 77 children 15 years or younger showed bilateral cysts in 14 and unilateral cysts in 4 of the children who had no detectable renal cysts using ultrasonography at baseline. Similar follow-up of 26 children 15 years or younger with unilateral cysts detected at baseline showed bilateral cysts in 17 children using ultrasonography. By 15 years of age, 181 patients in the total group of 420 showed bilateral cysts. Overall, 193 of 304 children (63.4%) who had follow-up at any age developed bilateral cysts detected using ultrasonography. Follow-up unavailable for all participants. The present results in 420 at-risk children with ADPKD 15 years or younger detected bilateral renal cysts using ultrasonography in 181 of the children who had a family history of this genetic disease.

Intraductal papillary–mucinous neoplasm of the pancreas associated with polycystic liver and kidney disease

A case of intraductal papillary-mucinous neoplasm (IPMN) of the pancreas associated with polycystic liver and kidney disease is reported. A 63-year-old man was admitted to hospital with heartburn and upper abdominal pain. CT indicated multiple cysts in the liver and bilateral kidneys, and also showed multiple cystic lesions in the pancreatic head. Pancreatoduodenectomy was performed, and a pathological diagnosis of intraductal papillary-mucinous adenoma of branch duct type of the pancreas was made. He died of renal failure and hepatic failure due to recurrent cholangitis 12 years after the operation. An autopsy confirmed multiple cysts in the liver and kidneys. Multiple hepatic cysts were lined by biliary-type epithelium with no connection to the bile ducts. Peribiliary cysts were observed, and histology of the liver indicated von Meyenburg complexes. The kidneys showed that the cysts originated from all segments of the renal tubule. The autopsy findings suggested that the patient had suffered from autosomal-dominant polycystic kidney disease (ADPKD), but he did not have a family history of ADPKD. This case demonstrates that IPMN of the pancreas can occur as an extrarenal complication in patients with polycystic liver and kidney disease.

Pretransplant Genetic Testing of Live Kidney Donors at Risk for Autosomal Dominant Polycystic Kidney Disease

Pretransplant Genetic Testing of Live Kidney Donors at Risk for Autosomal Dominant Polycystic Kidney Disease

Phenotypic heterogeneity in pediatric autosomal dominant polycystic kidney disease at first presentation: a single-center, 20-year review.

The presentation of autosomal dominant polycystic kidney disease (ADPKD) in childhood provides an insight into comorbidities and potential areas for interventions and investigation. Phenotypic heterogeneity at the time of first presentation was studied with respect to age of diagnosis, mode of presentation, parental inheritance pattern, renal function, associated hypertension, and hyperlipidemia. Fifty-five children (median age of presentation, 8.7 years; 27% < 1 year) with ADPKD from 44 families followed up between March 1983 and March 2003 were reviewed. The diagnosis was based on family history and ultrasound confirmation of cysts. Progression of renal disease was followed over the study period (mean duration of follow-up, 4.9 years). A family history of ADPKD was known at presentation in 89%, which precipitated the screening diagnostic imaging in 59% of these children. Maternal inheritance was displayed in 51%, whereas 5% had no known family history of ADPKD. Bilateral renal findings were present in 78%. Hypertension (>95(th) percentile for age) was present in 22%, and hyperlipidemia was present in 54%. Renal function was not significantly diminished in 98% of patients with creatinine clearance > or =3rd percentile for age, and 7% had persistent proteinuria (>150 mg/d). No subjects had hepatic, splenic, or pancreatic cysts on ultrasound scan. A subpopulation of 10 patients had features of ADPKD dating back to prenatal ultrasound scans. All prenatal cases were characterized by bilateral renal findings, 90% had a known family history of ADPKD at the time of presentation, and 89% of these patients displayed maternal inheritance. Follow-up studies showed a persistence of hyperlipidemia despite pharmacotherapeutic treatment of hypertension, infrequent proteinuria, and sustained renal function in most patients. The results of this study show that many children at the time of first presentation have a significant prevalence of modifiable risk factors: hypertension, proteinuria, and hyperlipidemia, in the face of normal renal function. The results also show a unique presentation existing in prenatal subjects.

Screening a living kidney donor for polycystic kidney disease using heavily T2-weighted MRI

Autosomal dominant polycystic kidney disease (ADPKD) accounts for approximately 8% of those awaiting renal transplantation. Living related kidney donors for these patients require screening for ADPKD, most commonly by ultrasonography. Ultrasound has a negative predictive value (NPV) of 100% in patients aged older than 30 years, but only 96% for donors aged 20 to 30 years. This case shows that heavily T2-weighted magnetic resonance imaging (HT2MRI) may be a more sensitive screening method for ADPKD in younger kidney donors. Despite a normal screening ultrasound result, a kidney donor with a family history of ADPKD was found to have renal cysts intraoperatively, and the transplantation was canceled. Afterward, the donor was imaged with HT2MRI. In addition, the mathematical relationship between sensitivity, specificity, and NPV for ADPKD screening tests was derived. After the canceled transplantation, a second ultrasound still could not identify renal cysts. However, HT2MRI showed multiple small (~3-mm) cysts in both kidneys and a 2.5-cm cyst on the right kidney. Mathematical analysis showed that the NPV of a screening test for ADPKD was most closely related to sensitivity and that only tests with 100% sensitivity would have a 100% NPV. We conclude that ultrasound is not a sufficiently sensitive screening test for ADPKD in younger living related renal donors. HT2MRI has improved sensitivity and may be the best screening test for ADPKD in this population.