Kidneys and women's health: key challenges and considerations

The theme of World Kidney Day 2018 is 'kidneys and women's health: include, value, empower'. To mark this event, Nature Reviews Nephrology asked four leading researchers to discuss key considerations related to women's kidney health, including specific risk factors, as well as the main challenges and barriers to care for women with kidney disease and how these might be overcome. They also discuss policies and systems that could be implemented to improve the kidney health of women and their offspring and the areas of research that are needed to improve the outcomes of kidney disease in women

Urine protein concentration estimation for biomarker discovery

Recent advances have been made in the study of urinary proteomics as a diagnostic tool for renal disease and pre-eclampsia which requires accurate measurement of urinary protein. We compared different protein assays (Bicinchoninic acid (BCA), Lowry and Bradford) against the ‘gold standard’ amino-acid assay in urine from 43 women (8 non-pregnant, 34 pregnant, including 8 with pre-eclampsia. BCA assay was superior to both Lowry and Bradford assays (Bland Altman bias: 0.08) compared to amino-acid assay, which performed particularly poorly at higher protein concentrations. These data highlight the need to use amino-acid or BCA assays for unprocessed urine protein estimation

Hypertension during Pregnancy is Associated with Coronary Artery Calcium Independent of Renal Function

Abstract Background: Hypertension during pregnancy (HDP) increases the risk of future coronary heart disease (CHD), but it is unknown whether this association is mediated by renal injury. Reduced renal function is both a complication of HDP and a risk factor for CHD. Methods: Logistic regression models were fit to examine the association between a history of HDP and the presence and extent of coronary artery calcification (CAC), a measure of subclinical coronary artery atherosclerosis, in 498 women from the Epidemiology of Coronary Artery Calcification Study (mean age 63.3+/-9.3 years). Results: Fifty-two (10.4%) women reported a history of HDP. After adjusting for age at time of study participation, HDP was associated with increased serum creatinine later in life (p=0.014). HDP was positively associated with the presence of CAC after adjusting for age at time of study participation (OR=2.7, 95% CI 1.4-5.4). This association was slightly attenuated with adjustment for body size and blood pressure (OR=2.4, 95% CI 1.2-4.9) but was not further attenuated with adjustment for serum creatinine and urinary albumin/creatinine ratio (OR=2.6, 95% CI 1.3-5.3). Results were similar for CAC extent. Conclusions: HDP may increase a woman's risk of future CHD beyond traditional risk factors and renal function. Women with a history of HDP should be monitored for potential increased risk of CHD as they age.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78144/1/jwh.2008.1285.pd

Hypertension in Pregnancy Is a Risk Factor for Microalbuminuria Later in Life

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99687/1/jch12116.pd

Use of Machine Learning Consensus Clustering to Identify Distinct Subtypes of Black Kidney Transplant Recipients and Associated Outcomes

Importance: Among kidney transplant recipients, Black patients continue to have worse graft function and reduced patient and graft survival. Better understanding of different phenotypes and subgroups of Black kidney transplant recipients may help the transplant community to identify individualized strategies to improve outcomes among these vulnerable groups. Objective: To cluster Black kidney transplant recipients in the US using an unsupervised machine learning approach. Design, Setting, and Participants: This cohort study performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in Black kidney transplant recipients in the US from January 1, 2015, to December 31, 2019, in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Each cluster\u27s key characteristics were identified using the standardized mean difference, and subsequently the posttransplant outcomes were compared among the clusters. Data were analyzed from June 9 to July 17, 2021. Exposure: Machine learning consensus clustering approach. Main Outcomes and Measures: Death-censored graft failure, patient death within 3 years after kidney transplant, and allograft rejection within 1 year after kidney transplant. Results: Consensus cluster analysis was performed for 22 687 Black kidney transplant recipients (mean [SD] age, 51.4 [12.6] years; 13 635 men [60%]), and 4 distinct clusters that best represented their clinical characteristics were identified. Cluster 1 was characterized by highly sensitized recipients of deceased donor kidney retransplants; cluster 2, by recipients of living donor kidney transplants with no or short prior dialysis; cluster 3, by young recipients with hypertension and without diabetes who received young deceased donor transplants with low kidney donor profile index scores; and cluster 4, by older recipients with diabetes who received kidneys from older donors with high kidney donor profile index scores and extended criteria donors. Cluster 2 had the most favorable outcomes in terms of death-censored graft failure, patient death, and allograft rejection. Compared with cluster 2, all other clusters had a higher risk of death-censored graft failure and death. Higher risk for rejection was found in clusters 1 and 3, but not cluster 4. Conclusions and Relevance: In this cohort study using an unsupervised machine learning approach, the identification of clinically distinct clusters among Black kidney transplant recipients underscores the need for individualized care strategies to improve outcomes among vulnerable patient groups

The effect of early diagnosis and treatment on maternal and fetal outcomes in patients with HELLP syndrome

Uvod: Sindrom HELLP, težak oblik preeklampsije kojega klinički karakterizira hemoliza, povišeni jetreni enzimi, te mali broj trombocita, prvi je put opisan 1982. godine. Materijali i metode: Kako bismo procijenili utjecaj identificiranja ovoga sin-droma na ishode liječenja rodilja i fetusa, proveli smo retrospektivnu studiju i pregledali dokumentaciju bolesnica s preeklampsijom liječenih u Klinici Mayo prije i nakon 1982. godine. Načinili smo retrospektivnu dijagnozu sindroma HELLP u 11 od 146 bolesnica liječenih zbog preeklampsije prije 1982. godine. Usporedili smo ishode trudnoće u nasumce odabranoj skupini 24 žene sa sin-dromom HELLP koje su liječene u Klinici Mayo između 1986. i 1994. godine. Rezultati: Nismo zapazili statistički značajnu razliku među demografskim podatcima o rodiljama ili dijagnostičkim laboratorijskim nalazima. Smrtnost fetusa je bila značajno viša prije 1982. godine. Pojavnost i težina akutnog zatajenja bubrega i drugih skupnih komplikacija kod rodilja (uključujući plućni edem, pleuralni izljev, perikardijski izljev, unutarmoždano krvarenje, konvulzi-je, hepatičku nekrozu, te odignuće mrežnice) bili su značajno veći prije 1982. godine. Nakon te godine vrijeme od dijagnoze do porođaja bilo je značajno kraće (2,5 u odnosu na 14 dana), a za bolesnice je bilo vjerojatnije da će pri-miti profilaksu protiv konvulzija magnezijevim sulfatom. Zabilježena je i tendencija većega broja carskih rezova i poticanja trudova u žena liječenih nakon 1982. godine. Zaključci: Navedena zapažanja ukazuju da je prepoznavanje sindroma HELLP kao zasebnoga kliničkog sindroma dovelo do poboljšanih ishoda trudnoće vjerojatno zbog pravodobnije dijagnoze i ranijeg završetka trudnoće.Background: HELLP syndrome, a severe form of preeclampsia clinically characterized by hemolysis, elevated liver enzymes, and low platelet count, was first described in 1982. Materials and Methods: To assess the impact of recognition of this syndrome on fetal and maternal outcomes, we conducted a retrospective study and reviewed the records of patients with preeclampsia treated at Mayo Clinic before and after 1982. We made a retrospective diagnosis of HELLP in 11 of 146 patients treated for preeclampsia prior to 1982. We compared pregnancy outcomes to a randomly selected group of 24 women with HELLP syndrome treated at Mayo Clinic between 1986 and 1994. Results: We did not observe a statistically significant difference in maternal demographics or diagnostic laboratory findings. Priorto 1982, fetal mortality was significantly higher. The incidence and severity of acute renal failure and other cumulative maternal complications (including pulmonary edema, pleural effusion, pericardial effusion, intracerebral hemorrhage, seizure, hepatic necrosis, and retinal detachment) were significantly higher priorto 1982. After 1982, the time from diagnosis to delivery was significantly shorter (2.5 vs. 14 days), and patients were more likely to receive seizure prophylaxis with magnesium sulfate. There was a trend towards more Caesarian sections and labor induction in women treated after 1982. Conclusions: These observations suggest that recognition of HELLP as a distinct clinical syndrome has led to improved outcomes of pregnancies, probably due to more timely diagnosis and earlier termination of pregnancy

Loss of placental growth factor ameliorates maternal hypertension and preeclampsia in mice

Preeclampsia remains a clinical challenge due to its poorly understood pathogenesis. A prevailing notion is that increased placental production of soluble fms-like tyrosine kinase-1 (sFlt-1) causes the maternal syndrome by inhibiting proangiogenic placental growth factor (PlGF) and VEGF. However, the significance of PlGF suppression in preeclampsia is uncertain. To test whether preeclampsia results from the imbalance of angiogenic factors reflected by an abnormal sFlt-1/PlGF ratio, we studied PlGF KO (Pgf-/-) mice and noted that the mice did not develop signs or sequelae of preeclampsia despite a marked elevation in circulating sFLT-1. Notably, PlGF KO mice had morphologically distinct placentas, showing an accumulation of junctional zone glycogen. We next considered the role of placental PlGF in an established model of preeclampsia (pregnant catechol-O-methyltransferase-deficient [COMT-deficient] mice) by generating mice with deletions in both the Pgf and Comt genes. Deletion of placental PlGF in the context of COMT loss resulted in a reduction in maternal blood pressure and increased placental glycogen, indicating that loss of PlGF might be protective against the development of preeclampsia. These results identify a role for PlGF in placental development and support a complex model for the pathogenesis of preeclampsia beyond an angiogenic factor imbalance

Flash Pulmonary Edema in a Patient With Unilateral Renal Artery Stenosis and Bilateral Functioning Kidneys

Flash pulmonary edema typically exhibits sudden onset and resolves rapidly. It generally is associated with bilateral renal artery stenosis or unilateral stenosis in conjunction with a single functional kidney. We describe a patient who presented with flash pulmonary edema treated by percutaneous therapy with stent implantation. Our case is unique in that the flash pulmonary edema occurred in the setting of unilateral renal artery stenosis with bilateral functioning kidneys

Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

ContextPreeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.ObjectiveTo investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44.Design and interventionFKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling.Settings and participantsHuman samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid.Main outcome measuresPreeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed.ResultsThe CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis.ConclusionsThe FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes