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2.
Kidney360 ; 4(12): 1806-1815, 2023 12 01.
Article in English | MEDLINE | ID: mdl-38010035

ABSTRACT

Patients with autosomal dominant polycystic kidney disease benefit from specialized care over their lifetimes, starting with diagnosis of the condition with ongoing discussion of both the renal course and extra-renal issues. Both renal and extra-renal issues may continue to cause major morbidity even after successful kidney transplant or initiation of RRT, and extra-renal disease aspects should always be considered as part of routine management. In this review, we will focus on updates in pain/depression screening, cardiac manifestations, liver and pancreatic cysts, kidney stone management, and genetic counseling. In some instances, we have shared our current clinical practice rather than an evidence-based guideline. We anticipate more standardization of care after the release of the Kidney Disease Improving Global Outcomes guidelines for management in autosomal dominant polycystic kidney disease later this year.


Subject(s)
Kidney Calculi , Kidney Transplantation , Polycystic Kidney, Autosomal Dominant , Humans , Polycystic Kidney, Autosomal Dominant/diagnosis , Polycystic Kidney, Autosomal Dominant/therapy , Kidney , Patient Care
3.
Am J Nephrol ; 54(7-8): 329-336, 2023.
Article in English | MEDLINE | ID: mdl-37253348

ABSTRACT

INTRODUCTION: Kidney stone type varies with age, sex, season, and medical conditions. Lower estimate glomerular filtration rate (eGFR) leads to changes in urine chemistry, and risk factors for kidney stones are thought to vary by stone type. We explore the association between eGFR, urine risk factors, and common stone compositions. METHODS: This was a retrospective cohort study of 811 kidney stone patients seen at Yale Medicine between 1994 and 2021 with serum chemistries and 24-h urine chemistries matched within 1 year of baseline stone analysis. Patients' eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation. Demographics and medical history were compared by χ2 tests. 24-h urine chemistries and stone analyses were analyzed by one-way ANOVA. Linear regressions were performed to control for demographics, comorbidities, and stone composition. RESULTS: With lower eGFR, the proportion of calcium stones declined while uric acid (UA) stones increased. On univariable analysis, lower eGFR was associated with lower urine pH, calcium, citrate, UA, magnesium, phosphorus, and ammonium. On multivariable analysis, controlling for age, sex, ethnicity, body mass index, comorbidities, and stone type, these factors remained significant. Stone formers with lower eGFR had elevated supersaturation for UA, but reduced supersaturations for calcium-containing stones. Though urine oxalate was significant on univariable analysis, it was not on multivariable analysis. CONCLUSION: Changes in urine parameters are strongly correlated with eGFR regardless of stone type. Renal function may play a key role in modulating kidney stone risk factors. Strategies to mitigate stone risk may need to vary with kidney function, especially when patient urine or stone composition data are unavailable.


Subject(s)
Calcium , Kidney Calculi , Humans , Retrospective Studies , Kidney Calculi/epidemiology , Kidney Calculi/etiology , Risk Factors , Kidney
4.
Alcohol Clin Exp Res ; 45(11): 2231-2245, 2021 11.
Article in English | MEDLINE | ID: mdl-34585391

ABSTRACT

BACKGROUND: Few studies have examined the association between APOE genotype and alcohol use. Although some of these studies have reported outcomes associated with a history of drinking, none have examined alcohol-seeking behavior. In addition, no preclinical studies have examined alcohol use as a function of APOE genotype with or without traumatic brain injury. METHODS: Male and female human APOE3- and APOE4-targeted replacement (TR) mice were used to assess voluntary alcohol seeking longitudinally using a 2-bottle choice paradigm conducted within the automated IntelliCage system prior to and following repeated mild TBI (rmTBI). Following an acquisition phase in which the concentration of ethanol (EtOH) was increased to 12%, a variety of drinking paradigms that included extended alcohol access (EAA1 and EAA2), alcohol deprivation effect (ADE), limited access drinking in the dark (DID), and progressive ratio (PR) were used to assess alcohol-seeking behavior. Additional behavioral tasks were performed to measure cognitive function and anxiety-like behavior. RESULTS: All groups readily consumed increasing concentrations of EtOH (4-12%) during the acquisition phase. During the EAA1 period (12% EtOH), there was a significant genotype effect in both males and females for EtOH preference. Following a 3-week abstinence period, mice received sham or rmTBI resulting in a genotype- and sex-independent main effect of rmTBI on the recovery of righting reflex and a main effect of rmTBI on spontaneous home-cage activity in females only. Reintroduction of 12% EtOH (EAA2) resulted in a significant effect genotype for alcohol preference in males with APOE4 mice displaying increased preference and motivation for alcohol compared with APOE3 mice independent of TBI while in females, there was a significant genotype × TBI interaction under the ADE and DID paradigms. Finally, there was a main effect of rmTBI on increased risk-seeking behavior in both sexes, but no effect on spatial learning or cognitive flexibility. CONCLUSION: These results suggest that sex and APOE genotype play a significant role in alcohol consumption and may subsequently influence long-term recovery following traumatic brain insults.


Subject(s)
Alcohol Drinking/metabolism , Apolipoproteins E/metabolism , Behavior, Addictive/metabolism , Genotype , Alcohol Drinking/genetics , Animals , Apolipoproteins E/genetics , Behavior, Addictive/genetics , Conditioning, Classical/physiology , Female , Humans , Male , Mice
6.
Diabetes Metab Syndr Obes ; 3: 431-7, 2010 Dec 06.
Article in English | MEDLINE | ID: mdl-21437113

ABSTRACT

PURPOSE: To assess the effects of topiramate on C-fiber function, nerve fiber morphology, and metabolism (including insulin sensitivity, obesity, and dyslipidemia) in type 2 diabetes. PATIENTS AND METHODS: We conducted an 18-week, open-label trial treating patients with topiramate. Twenty subjects with type 2 diabetes and neuropathy (61.5 ± 1.29 years; 15 male, 5 female) were enrolled and completed the trial. Neuropathy was evaluated by total neuropathy scores, nerve conduction studies, quantitative sensory tests, laser Doppler skin blood flow, and intraepidermal nerve fibers in skin biopsies. RESULTS: Topiramate treatment improved symptoms compatible with C-fiber dysfunction. Weight, blood pressure, and hemoglobin A(1c) also improved. Laser Doppler skin blood flow improved significantly after 12 weeks of treatment, but returned to baseline at 18 weeks. After 18 weeks of treatment there was a significant increase in intraepidermal nerve fiber length at the forearm, thigh, and proximal leg. Intraepidermal nerve fiber density was significantly increased by topiramate in the proximal leg. CONCLUSION: This study is the first to demonstrate that it is possible to induce skin intraepidermal nerve fiber regeneration accompanied by enhancement of neurovascular function, translating into improved symptoms as well as sensory nerve function. The simultaneous improvement of selective metabolic indices may play a role in this effect, but this remains to be determined.

7.
Diabetes Care ; 30(4): 896-902, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17392551

ABSTRACT

OBJECTIVE: Diabetes leads to protein kinase C (PKC)-beta overactivation and microvascular dysfunction, possibly resulting in disordered skin microvascular blood flow (SkBF) and other changes observed in diabetic peripheral neuropathy (DPN) patients. We investigate the effects of the isoform-selective PKC-beta inhibitor ruboxistaurin mesylate on neurovascular function and other measures of DPN. RESEARCH DESIGN AND METHODS: Endothelium-dependent and C fiber-mediated SkBF, sensory symptoms, neurological deficits, nerve fiber morphometry, quantitative sensory and autonomic function testing, nerve conduction studies, quality of life (using the Norfolk Quality-of-Life Questionnaire for Diabetic Neuropathy [QOL-DN]), and adverse events were evaluated for 20 placebo- and 20 ruboxistaurin-treated (32 mg/day) DPN patients (aged > or =18 years; with type 1 or type 2 diabetes and A1C < or =11%) during a randomized, double-masked, single-site, 6-month study. RESULTS: Endothelium-dependent (+78.2%, P < 0.03) and C fiber-mediated (+56.4%, P < 0.03) SkBF at the distal calf increased from baseline to end point. Significant improvements from baseline within the ruboxistaurin group were also observed for the Neuropathy Total Symptom Score-6 (NTSS-6) (3 months -48.3%, P = 0.01; end point -66.0%, P < 0.0006) and the Norfolk QOL-DN symptom subscore and total score (end point -41.2%, P = 0.01, and -41.0, P = 0.04, respectively). Between-group differences in baseline-to-end point change were observed for NTSS-6 total score (placebo -13.1%; ruboxistaurin -66.0%, P < 0.03) and the Norfolk QOL-DN symptom subscore (placebo -4.0%; ruboxistaurin -41.2%, P = 0.041). No significant ruboxistaurin effects were demonstrated for the remaining efficacy measures. Adverse events were consistent with those observed in previous ruboxistaurin studies. CONCLUSIONS: In this cohort of DPN patients, ruboxistaurin enhanced SkBF at the distal calf, reduced sensory symptoms (NTSS-6), improved measures of Norfolk QOL-DN, and was well tolerated.


Subject(s)
Diabetic Neuropathies/drug therapy , Enzyme Inhibitors/therapeutic use , Indoles/therapeutic use , Maleimides/therapeutic use , Microcirculation/physiology , Protein Kinase C/antagonists & inhibitors , Regional Blood Flow/drug effects , Skin/blood supply , Aged , Blood Flow Velocity , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Diabetic Neuropathies/diagnosis , Female , Humans , Male , Microcirculation/drug effects , Middle Aged , Placebos , Protein Kinase C beta , Racial Groups
8.
Metab Syndr Relat Disord ; 3(2): 113-21, 2005.
Article in English | MEDLINE | ID: mdl-18370718

ABSTRACT

BACKGROUND: The etiology of sensory neuropathies is often not found. We tested the hypothesis that the metabolic syndrome (MS) may be associated with painful neuropathy, in the absence of frank diabetes. METHODS: Clinical and quantitative neuropathy assessments were performed on 10 neuropathy patients with MS, 20 with MS with type 2 diabetes (10 recent onset and 10 of >5 years in duration), and 10 healthy, age-matched subjects. Intraepidermal nerve fiber density (IENF) and mean dendrite length (MDL) were determined by quantitative immunofluorescence on skin biopsies using antibody to PGP 9.5. RESULTS: In metabolic syndrome, MDL was reduced and correlated negatively with sensory symptoms, signs, HDL-C, and sural nerve amplitude. The strongest inverse metabolic correlate of the metabolic syndrome neuropathy was HDL-C, which also correlated negatively with sensory symptoms, signs, and sural nerve amplitudes. The strongest metabolic correlate of diabetic sensorimotor neuropathy was HbA1c, which was associated with reduced IENF in patients with >5 years in duration of disease as well as reduced peroneal nerve amplitudes. CONCLUSIONS: These data indicate that metabolic features, including HDL-C in metabolic syndrome, are associated with small fiber neuropathy and that MDL is an early marker of sensory neuropathy in patients with MS. Reductions in IENF reflect a longer duration of diabetes, with hyperglycemia leading to a sensorimotor neuropathy. These findings support the possibility that there is a sensory neuropathy with reduced intraepidermal nerve fiber length, which cosegregates with features of metabolic syndrome.

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