Faculty Bibliography
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Management of Coronary Disease in Patients with Advanced Kidney Disease
BACKGROUND:Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS:We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS:At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03). CONCLUSIONS:Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).
PMID: 32227756
ISSN: 1533-4406
CID: 5451232
Prevalence of low molecular weight proteinuria and Dent disease 1 CLCN5 mutations in proteinuric cohorts
BACKGROUND:Dent disease type 1 (DD1) is a rare X-linked disorder caused mainly by CLCN5 mutations. Patients may present with nephrotic-range proteinuria leading to erroneous diagnosis of focal segmental glomerulosclerosis (FSGS) and unnecessary immunosuppressive treatments. METHODS:M/TP, and A/TP from the CKiD cohort were compared with DD1 and DC. RESULTS:M/Cr of ≥ 120 mg/g (> 13.6 mg/mmol) creatinine were good screens for Dent disease. CONCLUSIONS:M/Cr ≥ 120 mg/g (> 13.6 mg/mmol) had the highest sensitivity and specificity when differentiating DD1 and studied CKiD populations.
PMID: 30852663
ISSN: 1432-198x
CID: 3732872
Uronephrology: a new nephrology subspecialty
PMID: 31895164
ISSN: 1473-6543
CID: 4252462
Nephrolithiasis in women: how different from men?
PURPOSE OF REVIEW/OBJECTIVE:Men have more kidney stones compared with women; however, the difference is progressively decreasing. The reasons for higher prevalence of stones in men, as well as increasing prevalence in women, is a subject of ongoing speculation. In this review, we summarize the evidence of differences between men and women and expand on the speculative causes. RECENT FINDINGS/RESULTS:Stone incidence is rising in women and adolescent girls. Stone disease is more heritable among men than women, and women demonstrate greater influence of the unique environment. Women under the age of 50 years who have been pregnant, have more than double the odds of kidney stones compared with those who have never been pregnant. Women are more burdened with obesity, bariatric surgery and dieting, all associated with increased stones. Women have higher urinary pH because of greater absorption of dietary organic anions leading to increased urinary citrate, compared with men, and they differ in tubular calcium handling. SUMMARY/CONCLUSIONS:It is obvious that the cause of stones in men and women is complex and requires further study. Potential clues offered are in the change of the female environment, influencing increasing incidence in stones, particularly of younger women and female adolescents.
PMID: 31789849
ISSN: 1473-6543
CID: 4217972
Medical evaluation of living kidney donors with nephrolithiasis: a survey of practices in the United States
BACKGROUND:A scarcity of organs has driven the transplant community to broaden selection criteria for both living and deceased donors. Living donor transplants offer better patient and allograft survival when compared with deceased donor transplants. Many transplant centers now allow complex living donors such as those with nephrolithiasis to undergo nephrectomy. METHODS:We conducted a survey of medical and surgical directors of kidney transplant programs in the United States to shed light on current practices pertaining to medical evaluation of living kidney donors with nephrolithiasis. 353 surveys were e-mailed to medical directors and surgical directors of transplant programs after contacts were obtained from UNOS. RESULTS:49 completed surveys were returned (13.9%). 77.7% (38/49) of survey participants said their centers will consider living kidney donor candidates with a history of symptomatic kidney stones, 69.4% (34/49) said their centers will consider candidates who are incidentally found to have kidney stones and 10.2% (5/49) said their centers decline all potential donors with nephrolithiasis. CONCLUSIONS:Several programs are still reluctant to allow potential donors with nephrolithiasis to donate. There is an unmet need to develop evidence-based guidelines to optimize outcomes in this population of kidney donors with nephrolithiasis and their recipients.
PMID: 31696378
ISSN: 1437-7799
CID: 4179472
Occupational kidney stones
PURPOSE OF REVIEW/OBJECTIVE:Kidney stones are a common and preventable disorder. Certain occupations may increase risk for stone disease which will be discussed in this review. Few observational studies have examined this association. RECENT FINDINGS/RESULTS:Some occupations prevent individuals from drinking enough fluids to maintain a dilute urine or to void when they need to. People may have poor access to fluids or to bathroom facilities. These issues pose a risk for stone disease and are exacerbated by those who work in warmer climates. Individuals who do more activity while working, especially outdoors, perspire more, leading to more concentrated urine. In more sedentary jobs, individuals are at a higher risk of metabolic syndrome and therefore have a higher risk for stones. Astronauts, who work in environments without gravity, mobilize calcium from bone, leading to a higher risk of stone disease. SUMMARY/CONCLUSIONS:Proper fluid intake, more access to restrooms and increased use of potassium citrate may be the best options for those who encounter greater risk for stones because of their occupation.
PMID: 31895162
ISSN: 1473-6543
CID: 4252452
Sex differences in the temperature dependence of kidney stone presentations: a population-based aggregated case-crossover study
Previous studies assumed a uniform relationship between heat and kidney stone presentations. Determining whether sex and other characteristics modify the temperature dependence of kidney stone presentations has implications for explaining differences in nephrolithiasis prevalence and improving projections of the effect of climate change on nephrolithiasis. We performed an aggregated case-crossover study among 132,597 children and adults who presented with nephrolithiasis to 68 emergency departments throughout South Carolina from 1997 to 2015. We used quasi-Poisson regression with distributed lag non-linear models to estimate sex differences in the cumulative exposure and lagged response between maximum daily wet-bulb temperatures and emergent kidney stone presentations, aggregated at the ZIP-code level. We also explored interactions by age, race, payer, and climate. Compared to 10 °C, daily wet-bulb temperatures at the 99th percentile were associated with a greater increased relative risk (RR) of kidney stone presentations over 10 days for males (RR 1.73; 95% CI 1.56, 1.91) than for females (RR 1.15; 95% CI 1.01, 1.32; interaction P < 0.001). The shape of the lagged response was similar for males and females, with the greatest risk estimated for the 2 days following high temperatures. There were weak differences by age, race, and climatic zone, and no differences by payer status. The estimated risk of presenting emergently with kidney stones within 10 days of high daily wet-bulb temperatures was substantially greater among men than women, and similar between patients with public and private insurance. These findings suggest that the higher risk among males may be due to sexually dimorphic physiologic responses rather than greater exposure to ambient temperatures.
PMID: 30900001
ISSN: 2194-7236
CID: 3735302
The Association of Mesalamine With Kidney Disease
The package inserts for products containing 5-aminosalicylic acid, or mesalamine, include the following language regarding the risk of adverse kidney effects: "renal impairment, including minimal change nephropathy, acute and chronic interstitial nephritis, and rarely renal failure, has been reported in patients given products such as mesalamine delayed-release tablets that contain mesalamine or are converted to mesalamine." In this article, we review the data regarding this nephrotoxicity and the recommendations regarding appropriate monitoring. Chronic interstitial nephritis is a rare occurrence in patients treated with these drugs for Crohn disease and ulcerative colitis. Patients often present with asymptomatic reductions in glomerular filtration rate, without accompanying pyuria, skin lesions, or eosinophilia, unlike cases of acute interstitial nephritis. Drug cessation is usually associated with improved kidney function. However, if left undetected, more prolonged exposure to the drug can lead to irreversible kidney failure and end-stage kidney disease. No convincing studies demonstrate efficacy of treatment with corticosteroids. Frequent monitoring of serum creatinine, especially in the first years after initiation of therapy, is recommended.
PMID: 32147005
ISSN: 1548-5609
CID: 4349582
Use of tablo hemodialysis systems to extend dialytic capabilities for the COVID-19-associated surge of AKI [Meeting Abstract]
Background: The COVID-19 pandemic was associated with a greater incidence of AKI than expected. At the NY Harbor VA we faced an overwhelming number of AKI patients who were critically ill with multi-organ failure. We needed to invoke new mechanisms of providing kidney replacement therapy (KRT).
Method(s): We obtained 3 Tablo systems in late March, 2019. The machines have selfcontained reverse osmosis capabilities and so do not require other equipment to operate. They can make dialysate from concentrate and tap water and so do not require special plumbing adaptation. Their self-contained step-by-step procedures are relatively simple to follow and allow rapid training of previously unskilled personnel. Tablo generates 300 ml dialysate per minute, and blood flow was increased to up to 400 ml/min as tolerated.
Result(s): Training was completed by 2 nephrologists and 2 RNs without previous dialysis experience. We used the Tablo Hemodialysis System to provide KRT to critically ill patients. In the first week we demonstrated that water cultures and endotoxin testing were negative, and that AAMI water tests were acceptable. We used the machines to provide KRT for ICU patients with double-lumen dialysis catheters. In addition we used the machines on hospital wards where KRT had not been provided before because of a lack of the plumbing needs of conventional HD machines. We provided multiple treatments 3-6 times per week for 15 AKI patients, mean age 65 years. The mean of the best urea reduction ratio achieved in the first 1-4 treatments, if available, was 41% (often limited by hypotension and fulfillment of ultrafiltration, UF, needs). Most treatments were successful and were slowed for hypotension or tachycardia. Some were aborted because of water pressure alarms if sediment filters needed replacement, or lines clotted due to hypercoagulability associated with COVID-19. Personnel availability dictated that most treatments were 3-4 hours (and up to 8h), and generally achieved UF goals. Later HD nurses cannulated arteriovenous fistulas in ESKD patients and left treatment to non-HD nurses to complete.
Conclusion(s): By incorporating a user-friendly platform and an accelerated training program including nephrologists and RNs without previous dialysis experience, we were able to nearly double our capacity to deliver KRT during the surge
Method(s): We obtained 3 Tablo systems in late March, 2019. The machines have selfcontained reverse osmosis capabilities and so do not require other equipment to operate. They can make dialysate from concentrate and tap water and so do not require special plumbing adaptation. Their self-contained step-by-step procedures are relatively simple to follow and allow rapid training of previously unskilled personnel. Tablo generates 300 ml dialysate per minute, and blood flow was increased to up to 400 ml/min as tolerated.
Result(s): Training was completed by 2 nephrologists and 2 RNs without previous dialysis experience. We used the Tablo Hemodialysis System to provide KRT to critically ill patients. In the first week we demonstrated that water cultures and endotoxin testing were negative, and that AAMI water tests were acceptable. We used the machines to provide KRT for ICU patients with double-lumen dialysis catheters. In addition we used the machines on hospital wards where KRT had not been provided before because of a lack of the plumbing needs of conventional HD machines. We provided multiple treatments 3-6 times per week for 15 AKI patients, mean age 65 years. The mean of the best urea reduction ratio achieved in the first 1-4 treatments, if available, was 41% (often limited by hypotension and fulfillment of ultrafiltration, UF, needs). Most treatments were successful and were slowed for hypotension or tachycardia. Some were aborted because of water pressure alarms if sediment filters needed replacement, or lines clotted due to hypercoagulability associated with COVID-19. Personnel availability dictated that most treatments were 3-4 hours (and up to 8h), and generally achieved UF goals. Later HD nurses cannulated arteriovenous fistulas in ESKD patients and left treatment to non-HD nurses to complete.
Conclusion(s): By incorporating a user-friendly platform and an accelerated training program including nephrologists and RNs without previous dialysis experience, we were able to nearly double our capacity to deliver KRT during the surge
EMBASE:633704127
ISSN: 1533-3450
CID: 4750162
Primary hyperoxaluria (PH) types 1 and 2 with kidney and/or liver transplant achieve best health-related quality of life (HRQOL) [Meeting Abstract]
Background: Our previous study showed that PH without a transplant (tx) had worse HRQoL compared to the US Standard Population and worsened with increased stone frequency. We now show the first longitudinal HRQoL profiles for PH patients with transplants.
Method(s): PH participants were enrolled from the Rare Kidney Stone Consortium registry. HRQoL was measured with a generic non-disease specific instrument (SF-36v2). Results were calculated as norm-based scores (NBS) based on US Standard Population (Mean domain score = 50). We created three groups based on the time of last stone event (<= 30 days, 31 - 365 days, >;366 days). The study compared HRQoL for participants with a kidney and/or liver transplant over 5 different time points.
Result(s): This sub-sample included 100 surveys of 32 PH participants (16 males and 16 females) with a tx. The mean age was 47 years for both males and females. This subsample includes 24 participants with liver/kidney tx (75%) and 8 with kidney tx only (25%). Participants with only a kidney tx reported significantly more stone events within a year (26% vs 13%, X2 =0.028). Two way ANOVA did not find a change in HRQoL profiles over time for PH participants with kidney or kidney/liver tx (figure). Most mean domain scores are 50 or above, except for the domain of General Health which was less. Participants with only a kidney tx scored significantly lower in role physical, bodily pain, general health, social function, and physical component score (data not shown) than participants with kidney/liver tx. There was no difference between male and female participants over time.
Conclusion(s): PH participants with kidney/liver tx achieve better HRQoL, measured with a non-disease specific generic instrument, than those with kidney alone; both are better when compared to the US Standard Population. The majority of PH participants with a tx are stone-free, with a direct beneficial impact on their HRQoL
Method(s): PH participants were enrolled from the Rare Kidney Stone Consortium registry. HRQoL was measured with a generic non-disease specific instrument (SF-36v2). Results were calculated as norm-based scores (NBS) based on US Standard Population (Mean domain score = 50). We created three groups based on the time of last stone event (<= 30 days, 31 - 365 days, >;366 days). The study compared HRQoL for participants with a kidney and/or liver transplant over 5 different time points.
Result(s): This sub-sample included 100 surveys of 32 PH participants (16 males and 16 females) with a tx. The mean age was 47 years for both males and females. This subsample includes 24 participants with liver/kidney tx (75%) and 8 with kidney tx only (25%). Participants with only a kidney tx reported significantly more stone events within a year (26% vs 13%, X2 =0.028). Two way ANOVA did not find a change in HRQoL profiles over time for PH participants with kidney or kidney/liver tx (figure). Most mean domain scores are 50 or above, except for the domain of General Health which was less. Participants with only a kidney tx scored significantly lower in role physical, bodily pain, general health, social function, and physical component score (data not shown) than participants with kidney/liver tx. There was no difference between male and female participants over time.
Conclusion(s): PH participants with kidney/liver tx achieve better HRQoL, measured with a non-disease specific generic instrument, than those with kidney alone; both are better when compared to the US Standard Population. The majority of PH participants with a tx are stone-free, with a direct beneficial impact on their HRQoL
EMBASE:633702956
ISSN: 1533-3450
CID: 4750122
