Although women with polycystic kidney disease (PKD) generally have healthy pregnancies and babies, pregnancy is associated with a greater risk of maternal complications and requires planning and ...management of their condition. Given these possible complications, routine communication about childbearing between women with PKD and their treating team is important. A question prompt list (QPL), a structured list of questions used by patients during consultations with healthcare providers, may be beneficial in assisting women with PKD to discuss their childbearing concerns with, and seek related information from, their treating team. The aims of this study were to co-design a QPL about pregnancy and childbearing for women with PKD, and evaluate its comprehensibility, salience, and acceptability.
An exploratory sequential mixed-methods study of women of reproductive age with PKD living in Australia, using an experience-based co-design approach with two phases. Women were recruited from a metropolitan public health service and via social media and invited to complete an anonymous online survey about the development of the PKD QPL (phase one) and participate in an online discussion group about its refinement (phase two).
Sixteen women completed the development survey and seven participated in the evaluation discussion group. Participants reported that women with PKD would value and use a QPL to prompt discussions with and seek further information about pregnancy and childbearing from their healthcare providers. Women identified four main topics for the QPL: 'thinking about having a baby', 'pregnancy', 'my medications' and 'after my baby is born'. Within each section a series of questions was developed. Based on the findings, a QPL about pregnancy and childbearing for women with PKD was co-designed.
Women with PKD often find it difficult to access information and have discussions with their health care providers about pregnancy and childbearing. The PKD QPL co-designed in this study was perceived to be an acceptable tool which will, from the perspectives of participants, assist women with PKD to access information more easily about pregnancy, childbearing and PKD; ask more targeted questions of their treating team; and make informed childbearing decisions.
Fertility rates, pregnancy, and maternal outcomes are not well described among women with a functioning kidney transplant. Using data from the Australian and New Zealand Dialysis and Transplant ...Registry, we analyzed 40 yr of pregnancy-related outcomes for transplant recipients. This analysis included 444 live births reported from 577 pregnancies; the absolute but not relative fertility rate fell during these four decades. Of pregnancies achieved, 97% were beyond the first year after transplantation. The mean age at the time of pregnancy was 29 +/- 5 yr. Compared with previous decades, the mean age during the last decade increased significantly to 32 yr (P < 0.001). The proportion of live births doubled during the last decade, whereas surgical terminations declined (P < 0.001). The fertility rate (or live-birth rate) for this cohort of women was 0.19 (95% confidence interval 0.17 to 0.21) relative to the Australian background population. We also matched 120 parous with 120 nulliparous women by year of transplantation, duration of transplant, age at transplantation +/-5 yr, and predelivery creatinine for parous women or serum creatinine for nulliparous women; a first live birth was not associated with a poorer 20-yr graft or patient survival. Maternal complications included preeclampsia in 27% and gestational diabetes in 1%. Taken together, these data confirm that a live birth in women with a functioning graft does not have an adverse impact on graft and patient survival.
Aims
To conduct an observational outcomes study examining pregnancy and neonatal outcomes of dialysed women aged 15–49, from 1966–2008, using data from the ANZDATA Registry.
Methods
Data from the ...ANZDATA Registry were captured and analysed from 1966–2008. Specific pregnancy outcomes included: live birth (LB), spontaneous abortion, stillbirth (SB) or termination of pregnancy. Delivery and neonatal outcomes, since 2001, were also analysed.
Results
There were 23 700 person‐years (PY) of observational data during the study period with 49 pregnancies, of which 30 (79%) resulted in a LB, once terminations were excluded. Pregnancy rates: Overall the pregnancy rate was 2.07 per 1000 PY for the study interval. A significant increase in the pregnancy rate was noted for the 1996–2008 time interval (3.3 per 1000 PY, compared with 0.54 and 0.67 in the eras 1976–1985 and 1986–1995, respectively; P = 0.004). Most pregnancies were observed in the 25–29 age group: 20–24, 25–29 and 30–34 (5.31, 5.61 and 3.87 per 1000 PY, respectively). Patients on peritoneal dialysis were less likely to achieve a pregnancy compared with haemodialysis patients (P < 0.02). Live birth rates: The overall LB rate was 1.26 per 1000 PY. The rate for each of the age brackets was as follows: 3.54 for 20–24, 3.61 for 25–29, and 2.39 per 1000 PY for 30–34, compared with 0 in the 15–19 group, and 1.22, 0.2 and 0.16 per 1000 PY among the groups 35–39, 40–44 and 45–49 years, respectively. LB rates were more favourable in the younger age groups. There was no significant era, disease, dialysis modality or race effect on LB rates. Excluding terminations, the LB rate was 79%. Age‐effect on pregnancy outcomes: Pregnancy outcome was not affected by age (mean ages shown): spontaneous abortions, 28.7 years (n = 3); LB, 29.3 years (n = 24); SB, 32.4 years (n = 5); terminations 30.6 years (n = 11). Maternal mortality and complications: The preeclampsia rate was 19.4% (6/31). No post‐partum maternal deaths were reported. Neonatal outcomes: Since 2001, 21 neonatal outcomes were reported. One baby developed polyhydramnios, one had a congenital malformation and one post‐natal death was reported. In total 53.4% were born preterm; 65% had a birthweight <2.5 kg (low birthweight) and 35% <1.5 kg (very low birthweight). Low birthweight correlated with prematurity.
Conclusion
Seventy‐nine per cent of women achieving a pregnancy in our cohort achieved a LB, although 53.4% of babies were born preterm and 65% were of low birthweight (<2.5 kg).
Summary at a Glance
This is an observational outcomes study examining pregnancy and neonatal outcomes of dialysed women aged 15–49, from 1966–2008, using data from the ANZDATA Registry. Seventy‐nine per cent of women achieving a pregnancy resulted in a live birth and 53.4% of babies were born preterm and 65% were of low birthweight.
Background
The international classification of diseases (ICD) code is frequently used to identify renal impairment in epidemiological research. However, Australian studies examining accuracy of this ...administrative data in coding kidney injury are lacking.
Aims
To compare the ICD 10 coding with the kidney disease: improving global outcomes (KDIGO) criteria in diagnosing acute kidney injury (AKI) and/or chronic kidney disease (CKD).
Methods
A retrospective study of 325 patients admitted to general medicine during January 2012 was performed. Sensitivity and specificity of ICD 10 in identifying AKI and CKD were calculated using KDIGO as gold standard.
Results
The sensitivities of ICD 10 in identifying AKI and CKD were low for both (59.5% and 54.1%), but the specificities were high (86.2% and 90.2%). Using KDIGO criteria, we identified 72 AKI (22%), 56 CKD (17%), 64 AKI on CKD (19%) and 133 controls (40%). Compared to the control group, patients with AKI and AKI on CKD had longer length of stay (3.2 vs 4.9 days and 3.2 vs 4.8 days, P = 0.20). Renal impairment groups had increased in‐hospital mortality rate (5% control, 6% AKI, 10% CKD, 9% AKI on CKD) and re‐admission rate within 30 days (13% control, 20% AKI, 25% CKD, 26% AKI on CKD). After adjusting for age, gender and comorbidities, the difference in outcomes was not statistically significant.
Conclusion
This study shows that ICD 10 fails to identify almost half of the patients with AKI (40.5%) and CKD (45.9%) in our cohort. A total of 60% had evidence of renal impairment as defined by KDIGO.
The AMP-activated protein kinase (AMPK) is a key controller of cellular energy metabolism. We studied its expression and regulation by salt handling in the kidney. Immunoprecipitation and Western ...blots of protein lysates from whole rat kidney using subunit-specific antibodies showed that the alpha1-catalytic subunit is expressed in the kidney, associated with the beta2- and either gamma1- or gamma2-subunits. Activated AMPK, detected by immunohistochemical staining for phospho-Thr172 AMPK (pThr172), was expressed on the apical surface of the cortical thick ascending limb of the loop of Henle, including the macula densa, and some parts of the distal convoluted tubule. Activated AMPK was also expressed on the basolateral surface of the cortical and medullary collecting ducts as well as some portions of the distal convoluted tubules. AMPK activity was increased by 25% in animals receiving a high-salt diet, and this was confirmed by Western blotting for pThr172. Low-salt diets were associated with reduced levels of the alpha-subunit of AMPK, which was highly phosphorylated on Thr172. Surprisingly, both low- and high-salt media transiently activated AMPK in the macula densa cell line MMDD1, an effect due to changes in osmolality, rather than Na+ or Cl- concentration. This study, therefore, demonstrates regulation of AMPK by both a high- and a low-salt intake in vivo and suggests a role for the kinase in the response to changes in osmolality within the kidney.
The following cases demonstrate a proof of concept for the safe and effective use of the glucagon‐like‐peptide‐1 receptor agonist (GLP‐1 RA) semaglutide for weight loss in obese, non‐diabetic, end ...stage kidney disease (ESKD) patients on haemodialysis (HD), who are unable to undergo renal transplantation due to obesity. Obesity is a common barrier to wait‐listing for renal transplantation with effective, broadly applicable weight loss strategies lacking. GLP‐1 RAs have been shown to be effective adjuncts to achieve weight loss in non‐diabetic obese people. However, the major clinical trials excluded patients with ESKD on dialysis. This paper outlines the successful use of semaglutide to achieve a target body mass index (BMI) prior to renal transplant wait‐listing in two obese, non‐diabetic, HD patients. These patients achieved a 16% and 12.6% weight loss in under 9 months with one now waitlisted and the other transplanted. This strategy has the potential for broader use in this patient cohort to improve wait‐list times by overcoming this common barrier to renal transplantation.
The profile of patients on chronic dialysis has shifted. There is a growing group of older patients with comorbid dementia and ESKD, who are at risk of overuse, underuse, and misuse of dialysis. ...Policy is lacking to help guide treatment decisions in this group. This paper explores clinical considerations specific to patients with comorbid ESKD and dementia. These include: the impact of comorbid dementia on dialysis effectiveness and feasibility; burden of care issues that are specific to patients with dementia; and capacity, autonomy, and consent. A better understanding of these issues may help guide discussions and decision making about treatment. For some older patients with multiple comorbidities including dementia, dialysis does not provide survival or quality of life benefit compared to medical management. These patients also experience additional treatment burden due to a ‘dementia unfriendly’ environment. However, exceptions may include patients who are younger, more independent, and have fewer comorbidities. Patients with dementia are often inappropriately assumed to lack capacity to participate in treatment decision making, and are at risk of having their preferences overlooked. Many patients with mild‐to‐moderate dementia remain capable of reporting their preferences and quality of life, and should always be involved in treatment discussions where possible.
The development of clinical treatment protocols usually relies on evidence-based guidelines that focus on randomized, controlled trials. For rare renal diseases, such stringent requirements can ...represent a significant challenge. Dense deposit disease (DDD; also known as membranoproliferative glomerulonephritis type II) is a prototypical rare disease. It affects only two to three people per million and leads to renal failure within 10 yr in 50% of affected children. On the basis of pathophysiology, this article presents a diagnostic and treatment algorithm for patients with DDD. Diagnostic tests should assess the alternative pathway of complement for abnormalities. Treatment options include aggressive BP control and reduction of proteinuria, and on the basis of pathophysiology, animal data, and human studies, plasma infusion or exchange, rituximab, sulodexide, and eculizumab are additional options. Criteria for treatment success should be prevention of progression as determined by maintenance or improvement in renal function. A secondary criterion should be normalization of activity levels of the alternative complement pathway as measured by C3/C3d ratios and C3NeF levels. Outcomes should be reported to a central repository that is now accessible to all clinicians. As the understanding of DDD increases, novel therapies should be integrated into existing protocols for DDD and evaluated using an open-label Bayesian study design.
The renal-specific NKCC2 (Na+-K+-2Cl- co-transporter 2) is regulated by changes in phosphorylation state, however, the phosphorylation sites and kinases responsible have not been fully elucidated. In ...the present study, we demonstrate that the metabolic sensing kinase AMPK (AMP-activated protein kinase) phosphorylates NKCC2 on Ser126 in vitro. Co-precipitation experiments indicated that there is a physical association between AMPK and the N-terminal cytoplasmic domain of NKCC2. Activation of AMPK in the MMDD1 (mouse macula densa-derived 1) cell line resulted in an increase in Ser126 phosphorylation in situ, suggesting that AMPK may phosphorylate NKCC2 in vivo. The functional significance of Ser126 phosphorylation was examined by mutating the serine residue to an alanine residue resulting in a marked reduction in co-transporter activity when exogenously expressed in Xenopus laevis oocytes under isotonic conditions. Under hypertonic conditions no significant change of activity was observed. Therefore the present study identifies a novel phosphorylation site that maintains NKCC2-mediated transport under isotonic or basal conditions. Moreover, the metabolic-sensing kinase, AMPK, is able to phosphorylate this site, potentially linking the cellular energy state with changes in co-transporter activity.
Alterations within the RAS (renin-angiotensin system) are pivotal for the development of renal disease. ACE2 (angiotensin-converting enzyme 2) is expressed in the kidney and converts the ...vasoconstrictor AngII (angiotensin II) into Ang-(1-7), a peptide with vasodilatory and anti-fibrotic actions. Although the expression of ACE2 in the diabetic kidney has been well studied, little is known about its expression in non-diabetic renal disease. In the present study, we assessed ACE2 in rats with acute kidney injury induced by STNx (subtotal nephrectomy). STNx and Control rats received vehicle or ramipril (1 mg. kg (-1) of body weight . day (-1), and renal ACE, ACE2 and mas receptor gene and protein expression were measured 10 days later. STNx rats were characterized by polyuria, proteinuria, hypertension and elevated plasma ACE2 activity (all P<0.01) and plasma Ang-(1-7) (P<0.05) compared with Control rats. There was increased cortical ACE binding and medullary mas receptor expression (P<0.05), but reduced cortical and medullary ACE2 activity in the remnant kidney (P<0.05 and P<0.001 respectively) compared with Control rats. In STNx rats, ramipril reduced blood pressure (P<0.01), polyuria (P<0.05)and plasma ACE2 (P<0.01), increased plasma Ang-(1-7) (P<0.001), and inhibited renal ACE(P<0.001). Ramipril increased both cortical and medullary ACE2 activity (P<0.01), but reduced medullary mas receptor expression (P<0.05). In conclusion, our results show that ACE2 activity is reduced in kidney injury and that ACE inhibition produced beneficial effects in association with increased renal ACE2 activity. As ACE2 both degrades AngII and generates the vasodilator Ang-(1-7), a decrease in renal ACE2 activity, as observed in the present study, has the potential to contribute to the progression of kidney disease.
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