47 research outputs found

    Genetic causes of hypercalciuric nephrolithiasis

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    Renal stone disease (nephrolithiasis) affects 3–5% of the population and is often associated with hypercalciuria. Hypercalciuric nephrolithiasis is a familial disorder in over 35% of patients and may occur as a monogenic disorder that is more likely to manifest itself in childhood. Studies of these monogenic forms of hypercalciuric nephrolithiasis in humans, e.g. Bartter syndrome, Dent’s disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels and receptors that are involved in regulating the renal tubular reabsorption of calcium. Thus, Bartter syndrome, an autosomal disease, is caused by mutations of the bumetanide-sensitive Na–K–Cl (NKCC2) co-transporter, the renal outer-medullary potassium (ROMK) channel, the voltage-gated chloride channel, CLC-Kb, the CLC-Kb beta subunit, barttin, or the calcium-sensing receptor (CaSR). Dent’s disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is due to mutations of the chloride/proton antiporter 5, CLC-5; ADHH is associated with activating mutations of the CaSR, which is a G-protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium–phosphate co-transporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia. These studies have provided valuable insights into the renal tubular pathways that regulate calcium reabsorption and predispose to hypercalciuria and nephrolithiasis

    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

    Genetics of hypercalciuric nephrolithiasis: renal stone disease.

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    Renal stone disease (nephrolithiasis) affects 5% of adults and is often associated with hypercalciuria. Hypercalciuric nephrolithiasis is a familial disorder in more than 35% of patients, and may occur as a monogenic disorder, or as a polygenic trait involving 3 to 5 susceptibility loci in man and rat, respectively. Studies of monogenic forms of hypercalciuric nephrolithiasis in man, for example, Bartter syndrome, Dent's disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels, and receptors that are involved in regulating the renal tubular reabsorption of calcium. Thus, Bartter syndrome, an autosomal recessive disease, is caused by mutations of the bumetanide-sensitive Na-K-Cl (NKCC2) cotransporter, the renal outer-medullary potassium channel (ROMK), the voltage-gated chloride channel, CLC-Kb, or in its beta subunit, Barttin. Dent's disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria, and nephrolithiasis, is due to mutations of the chloride/proton antiporter, CLC-5; ADHH is associated with activating mutations of the calcium-sensing receptor, which is a G protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium-phosphate cotransporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia. These studies have provided valuable insights into the renal tubular pathways that regulate calcium reabsorption and predispose to kidney stones and bone disease

    Administration of 75 mg of aspirin daily for 28 days is sufficient prophylaxis against renal transplant vein thrombosis.

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    INTRODUCTION: Early postoperative renal transplant vein thrombosis results in graft loss. We evaluate the effect of administering aspirin 75 mg daily for 28 days following transplantation. METHODS: Prospectively collected data on the outcome of all transplants undertaken in our unit in the five-year period from January 1997 to January 2002 were reviewed, and in cases of graft failure before three months the cause was defined. RESULTS: In the study period, a total of 401 transplants were undertaken (311 cadaveric and 90 living related). There was one case of renal transplant vein thrombosis (0.25%). This represents a significant reduction on the unit's historical incidence of 5.8%, P &lt; 0.001. CONCLUSION: Aspirin 75 mg daily is adequate to virtually abolish renal transplant vein thrombosis and has a role in thromboprophylaxis in other situations where heparin is contraindicated

    Parathyroidectomy is safe and improves symptoms in elderly patients with primary hyperparathyroidism (PHPT).

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    OBJECTIVE: Parathyroidectomy for primary hyperparathyroidism (PHPT) is curative in over 95% of cases. Although PHPT affects up to 2% of the elderly population, whose life expectancy may be a decade or more, such patients may be denied surgery because of perceived risk. This study investigates the outcomes of surgery for PHPT in the elderly. DESIGN AND PATIENTS: Consecutive patients with PHPT treated at a tertiary referral centre over 5 years. MEASUREMENTS: A prospective database recorded clinical, biochemical and pathological information. Pasieka's parathyroid symptom scores were obtained pre-operatively and post-operatively, from a recent subgroup of 70 consecutive patients. Deaths during follow-up were identified using the NHS Strategic Tracing Service. Statistical analysis was performed with spss v12.0. RESULTS: Between November 2002 and October 2007, 224 patients (17-89 years) underwent surgery for PHPT. In the subgroup comprising patients aged &gt;75 years there was a significantly greater proportion of women (47/56 vs. 52/81, P &lt; 0.05). Pre-operative indices of these patients were similar to younger patients, as were proportions undergoing minimally invasive parathyroidectomy (n = 134) or bilateral neck exploration (n = 90). Patients &gt;75 years had a longer hospital stay (1.6 vs. 0.8 days, P = 0.003). Pasieka's symptom scores improved significantly at 3-6 months postoperatively in all age groups. During a minimum median follow-up of 22 months, there were seven patients with persistent/recurrent disease. Median 2-year survival of those aged 60-74 and those over 75 ranged from 85-90%. CONCLUSION: Parathyroidectomy is safe in the elderly and is associated with a significant improvement in symptoms. As survival after operation is similar to younger patients, surgery should be considered in all elderly patients with PHPT

    Cost-effectiveness of scan-directed parathyroidectomy.

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    BACKGROUND: Concordant parathyroid localization with sestamibi and ultrasound scans allows minimally invasive parathyroidectomy (MIP) to be performed in patients with non-familial primary hyperparathyroidism (PHPT). AIM: To investigate the financial implications of scan-directed parathyroid surgery. METHODS: Analysis of hospital records for a cohort of consecutive unselected patients treated in a tertiary referral centre. RESULTS: Two hundred patients (138F:62M, age 18-91years) were operated for non-familial PHPT between Jan 2003 and Oct 2007. MIP was performed in 129 patients, with a mean operative time was 35 +/- 18min. Some 75 patients were discharged the same day and the others had a total of 72 in-patient days. Bilateral neck exploration (BNE) was performed in 71 patients with negative/non-concordant scans. Mean operative time was 58 +/- 25min. Only nine patients were discharged the same day and a total of 93 in-patient days were used ( approximately 1.3days/patient). The estimated total costs incurred were pound215,035 ( approximately 290,000). These costs would have been covered by the National Tariff ( pound2,170 per parathyroidectomy) but were higher than those possibly incurred if all 200 patients would have undergone BNE without any radiological investigations ( pound166,000 approximately 224,100euro). CONCLUSION: Shorter operative time and day-case admission for MIP generate costs savings that compensate only partially for the additional costs associated with parathyroid imaging studies.</euro
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