A summary of the 2023 Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) hypertension in pregnancy guideline.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.

Altered bowel habit and rectal bleeding in pregnancy: the importance of recognising undiagnosed inflammatory bowel disease.

Worsening of disease activity during pregnancy in patients with known inflammatory bowel disease, especially ulcerative colitis (UC), is well recognised, but the diagnosis of new-onset or previously undiagnosed UC in pregnancy has been inadequately studied to date. Recognition of gastrointestinal symptoms in pregnancy as potentially indicating UC is of paramount importance, as this allows appropriate investigation and instigation of therapies to optimise maternal and foetal outcomes. Here, we report three cases of women with gastrointestinal symptoms in pregnancy with disparate outcomes.

The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality.

BACKGROUND: Prognosis in chronic kidney disease (CKD) for adverse outcomes differs substantially based on the etiology of CKD. We examined whether the biomarker profile differed based on CKD etiology and whether they were associated with mortality. METHODS: Prospective observational study of 1,157 patients, 663 with diabetic kidney disease (DKD), 273 with glomerulonephritis (GN), and 221 with cystic/interstitial disease (polycystic kidney disease, pyelonephritis or chronic tubulointerstitial nephritis [PCK/TIN]) were identified in the Canadian Study of Prediction of Dialysis, Death and Interim Cardiovascular events over Time cohort. The outcome of interest was mortality before commencing dialysis. The biomarker profile consisted of N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I (TnI), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, high sensitivity C-reactive protein, fibroblast growth factor-23 (FGF23), transforming growth factor-beta, 25-hydroxylvitamin D, and cystatin C (CysC). RESULTS: The mean estimated glomerular filtration rate was 27 mL/min/1.73 m2 and median follow-up time was 44 months. Mortality before dialysis commencement was the greatest in DKD (20%), followed by PCK/TIN (13%), and was least in those GN (8%). The majority of deaths were cardiovascular in nature, 17, 9, and 5.5% for DKD, PCK/TIN, GN, respectively. Those with DKD had higher hazard for mortality, unadjusted (hazard ratio [HR] 2.7, 95% CI 1.7-4.3) and adjusted (HR 1.7, 95% CI 1.1-2.8). The biomarker profiles associated with mortality differed significantly by CKD etiology as follows: DKD was associated with CysC (HR 1.3, 95% CI 1.0-1.6), ADMA (HR 1.3, 95% CI 1.1-1.6), and NT-proBNP (HR 1.7, 95% CI 1.4-2.1), GN was associated with FGF23 (HR 1.8, 95% CI 1.1-2.8), TnI (HR 3.6, 95% CI 1.3-9.5), and transforming growth factor-beta (HR 0.6, 95% CI 0.4-0.9) and PCK/TIN was associated with ADMA (HR 1.5, 95% CI 1.3-1.8) and IL-6 (HR 2.1, 95% CI 1.5-3.1). CONCLUSIONS: Biomarkers profiles differ according to the etiology of CKD and are associated with mortality.

Mineral adaptations following kidney transplantation.

Klotho is predominantly expressed in the kidney and reported to have antioxidant and antifibrotic properties. Soluble Klotho (sKl), the circulating protein cleaved from membrane-bound Klotho, is reduced significantly with kidney disease and inversely associated with mortality. sKl has not been thoroughly evaluated prospectively after kidney transplantation. Incident kidney transplant recipients (KTRs) were prospectively evaluated pretransplantation, 1, 12 and 52 weeks post-transplantation. Basic biochemistry, sKl and intact FGF23 were measured. Within-subject comparisons were evaluated using repeat-measure anova or Friedman's analysis. Effects of immunosuppression and biochemical parameters on sKl and FGF-23 over time were analysed using mixed-effects modelling. Median serum creatinine (sCr) at 1 week was 116 (92-142) µmol/l, and at 52 weeks, all 29 KTRs had a functioning graft with median sCr of 111 (97-131) µmol/l. Compared with baseline, sKl was increased at 52 weeks following an initial decline at 1 week (P < 0.005 and P < 0.01, respectively), while FGF23 was considerably reduced at 52 weeks (P < 0.001). In a mixed-effects model, an increased sKl was not associated with reduction in immunosuppression or evaluated biochemical parameters. Modest increase in sKl is observed one-year postkidney transplantation with excellent early graft function suggesting factors beyond renal capacity may influence circulating sKl. FGF23 normalization was observed. Longer term evaluation in transplantation, specifically addressing the effects of immunosuppression, is required to understand the pathophysiology of the sKl/FGF23 axis and potential for modification.

Infection in advanced chronic kidney disease leads to increased risk of cardiovascular events, end-stage kidney disease and mortality.

The risk of infection in advanced chronic kidney disease (CKD) and its subsequent impact on adverse outcomes are not well established. Therefore, we determined the association of an infectious episode with the subsequent risk of cardiovascular ischemia, congestive heart failure, end-stage kidney disease or mortality in a Canadian prospective cohort (CanPREDDICT) of patients with advanced CKD (eGFR: 15-45 ml/min/1.73m(2)) followed by nephrologists for up to 5 years. Infectious episodes were classified by anatomic location and identified by positive culture, hospital admission, or use of antibiotics. Competing risk models were used to examine the time-varying risk of infection and the risk of cardiovascular ischemia, congestive heart failure, or end-stage kidney disease accounting for the competing risk of mortality. All outcomes were independently adjudicated. Of 2370 patients (mean age, 68 years; mean baseline eGFR, 28.2 mL/min/1.73m(2)), 575 patients (24.3%) had recorded infections; 378 had 1 infection episode, whereas 197 had 2 or more episodes, the most common being urinary and respiratory. An infectious episode was independently associated with an increased risk of cardiovascular ischemia (hazard ratio 1.80, 95% confidence interval 1.24-2.60), congestive heart failure (hazard ratio, 3.2; confidence interval, 2.25-4.61), end-stage kidney disease (hazard ratio, 1.58; confidence interval, 1.22-2.05) or mortality (hazard ratio, 3.39; confidence interval, 2.65-4.33). Thus, there is a high risk of infection in advanced CKD being associated with subsequent adverse outcomes.

Galactose therapy reduces proteinuria in patients with recurrent focal segmental glomerulosclerosis after kidney transplantation.

Primary focal segmental glomerulosclerosis is an important cause of end-stage kidney disease with a high rate of recurrent disease after kidney transplantation. Current therapy achieves remission in only half of patients. Recent interest has focused on the potential role of galactose in binding and inactivating the putative circulating permeability factor, supported by in vitro and clinical case report studies. Orally active and without major adverse effects, galactose has a favourable treatment profile compared with current immunosuppressive treatment options. We describe our experience using galactose therapy in two patients with recurrent focal segmental glomerulosclerosis after renal transplantation. Galactose was associated with symptomatic improvement and stabilization of graft function in one case; the other case was complicated by concurrent malignancy. In both cases, we observed a marked reduction in proteinuria with galactose treatment.

Multivariable risk model for postpartum re-presentation with hypertension: development phase.

OBJECTIVES: Postpartum hypertension is one of the leading causes of re-presentation to hospital postpartum and is associated with adverse long-term cardiovascular risk. Postpartum blood pressure monitoring and management interventions have been shown to reduce hospital re-presentation, complications and long-term blood pressure control. Identifying patients at risk can be difficult as 40%-50% present with de novo postpartum hypertension. We aim to develop a risk model for postpartum re-presentation with hypertension using data readily available at the point of discharge. DESIGN: A case-control study comparing all patients who re-presented to hospital with hypertension within 28 days post partum to a random sample of all deliveries who did not re-present with hypertension. Multivariable analysis identified risk factors and bootstrapping selected variables for inclusion in the model. The area under the receiver operator characteristic curve or C-statistic was used to test the model's discriminative ability. SETTING: A retrospective review of all deliveries at a tertiary metropolitan hospital in Melbourne, Australia from 1 January 2016 to 30 December 2020. RESULTS: There were 17 746 deliveries, 72 hypertension re-presentations of which 51.4% presented with de novo postpartum hypertension. 15 variables were considered for the multivariable model. We estimated a maximum of seven factors could be included to avoid overfitting. Bootstrapping selected six factors including pre-eclampsia, gestational hypertension, peak systolic blood pressure in the delivery admission, aspirin prescription and elective caesarean delivery with a C-statistic of 0.90 in a training cohort. CONCLUSION: The development phase of this risk model builds on the three previously published models and uses factors readily available at the point of delivery admission discharge. Once tested in a validation cohort, this model could be used to identify at risk women for interventions to help prevent hypertension re-presentation and the short-term and long-term complications of postpartum hypertension.

A comparison of the ocular features in Pierson and Alport syndrome: a case report and literature review.

BACKGROUND: Pierson syndrome and X-linked Alport syndrome result from pathogenic variants in LAMB2 and COL4A5, respectively, and both affect basement membranes in the kidney and the eye. This study describes the ocular features in an individual with a homozygous LAMB2 pathogenic variant and compares the reported abnormalities in Pierson syndrome with those in Alport syndrome. METHODS: A 28-year-old man who developed kidney failure 10 years previously and subsequently had an atrial septal defect repair was suspected of having genetic kidney disease on the basis of his likely diagnosis of Focal and Segmental Glomerulosclerosis (FSGS), his young age at presentation, and his cardiac anomaly. He then underwent Whole Exome Sequencing and a formal ophthalmological examination. RESULTS: The patient was found to have a homozygous Likely Pathogenic missense variant (p.(Arg1719Cys)) in LAMB2 consistent with the diagnosis of Pierson syndrome. He had normal visual acuity, normal optic globe and cornea size, and normal lens appearance on direct examination. Upon further testing, his cornea demonstrated central thinning. There was also increased corneal endothelial pleomorphism, a reduced foveal reflex, and a blunted foveal curvature, similar to the features seen in X-linked Alport syndrome. CONCLUSION: Our patient had a later onset form of Pierson syndrome or "FSGS type 5, with or without ocular abnormalities," consistent with his "milder" LAMB2 missense variant. The resemblance of the ocular features in Pierson syndrome and X-linked Alport syndrome suggests that mutations in LAMB2 and COL4A5 have similar effects on basement membranes and the pathogenesis of ocular damage.

Retinal Drusen Are More Common and Larger in Systemic Lupus Erythematosus With Renal Impairment.

Introduction: Complement has been implicated in systemic lupus erythematosus (SLE) pathogenesis on the basis of the associations with inherited complement defects and genome-wide association study risk alleles, glomerular deposits, reduced serum levels, and occasional reports of retinal drusen. This study examined drusen in SLE and their clinical significance. Methods: This cross-sectional observational study compared individuals with SLE recruited from renal and rheumatology clinics with hospital controls. Participants were reviewed for clinical features and underwent imaging with a nonmydriatic retinal camera. Deidentified images were examined by 2 trained graders for drusen number and size using a grid overlay. Results: The cohort with SLE (n = 65) comprised 55 women (85%) and 10 men (15%) with a median age of 47 years (interquartile range 35-59), where 23 (35%) were of southern European or Asian ancestry, and 32 (49%) had biopsy-proven lupus nephritis. Individuals with SLE had higher mean drusen numbers than controls (27 ± 60, 3 ± 9, respectively, P = 0.001), more drusen counts ≥10 (31, 48% and 3, 5%, respectively, P < 0.001), and more medium-large drusen (14, 22% and 3, 5%, respectively, P < 0.001). In SLE, mean drusen counts were higher, and drusen were larger, with an estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m2 (P = 0.02, P = 0.02, respectively) or class IV nephritis (P = 0.03, P = 0.02). Conclusion: Drusen composition resembles that of glomerular immune deposits. CFH controls complement activation in the extracellular matrix and CFH risk variants are shared by drusen in macular degeneration and by SLE. CFH represents a possible treatment target for SLE especially with renal impairment.

Increased retinal drusen in IgA glomerulonephritis are further evidence for complement activation in disease pathogenesis.

Drusen are retinal deposits comprising cell debris, immune material and complement that are characteristic of macular degeneration but also found in glomerulonephritis. This was a pilot cross-sectional study to determine how often drusen occurred in IgA glomerulonephritis and their clinical significance. Study participants underwent non-mydriatic retinal photography, and their deidentified retinal images were examined for drusen by two trained graders, who compared central drusen counts, counts ≥ 10 and drusen size with those of matched controls. The cohort comprised 122 individuals with IgA glomerulonephritis including 89 males (73%), 49 individuals (40%) of East Asian or Southern European ancestry, with an overall median age of 54 years (34-64), and median disease duration of 9 years (4-17). Thirty-nine (33%) had an eGFR < 60 ml/min/1.73 m2 and 72 had previously reached kidney failure (61%). Overall mean drusen counts were higher in IgA glomerulonephritis (9 ± 27) than controls (2 ± 7, p < 0.001). Central counts ≥ 10 were also more common (OR = 3.31 (1.42-7.73, p = 0.006), and were associated with longer disease duration (p = 0.03) but not kidney failure (p = 0.31). Larger drusen were associated with more mesangial IgA staining (p = 0.004). Increased drusen counts were also present in IgA glomerulonephritis secondary to Crohn's disease but not with Henoch-Schonlein purpura. The finding of retinal drusen in IgA glomerulonephritis is consistent with complement activation and represents a model for better understanding glomerular immune deposition and a supporting argument for treatment with anti-complement therapies.

Care for survivors of acute kidney injury.

BACKGROUND: The effects of acute kidney injury (AKI) extend beyond the acute illness phase. Patients who survive AKI are at increased risk of hospital readmission, chronic disease including kidney and cardiovascular disease, frailty and death. AKI may be overlooked among more obvious or complex healthcare concerns. While developing a cogent, systemic response to care after AKI is a neglected public health priority, attention to several common challenges may improve patient outcomes. OBJECTIVE: The aim of this article is to highlight common challenges in managing survivors of AKI and offer suggestions to guide management. DISCUSSION: For clinicians managing survivors of AKI, identifying and communicating patient priorities, risk factors and comorbidities including a history of AKI is important. Concurrent management challenges include education regarding lifestyle and pharmacotherapy, managing medication interruptions and dose adjustments, and re-establishing a long-term management plan for chronic diseases.

Diabetes Mellitus Following Renal Transplantation: Clinical and Pharmacological Considerations for the Elderly Patient.

Post-transplant diabetes mellitus occurs in 30-50% of cases during the first year post-renal transplantation. It is associated with increased morbidity, mortality and healthcare costs. Risk factors include age and specific immunosuppression regimens. At the same time, renal transplantation is increasingly indicated in elderly (aged >65 years) patients as this proportion of older patients in the prevalent dialysis population has increased. The immune system and ß cells undergo senescence and this impacts on the risk for developing post-transplant diabetes and our ability to prevent such development. It may, however, be possible to identify patients at risk of developing post-transplant diabetes, enabling treatment protocols that prevent or reduce the impact of post-transplant diabetes. Much work remains to be completed in this area and is facilitated by the growing base of knowledge regarding the pathophysiology of post-transplant diabetes. Should post-transplant diabetes develop, there are a range of treatment options available. There is increasing interest in using newer agents, although their safety and efficacy in transplant recipients remains to be conclusively established.

The Variability of Estimated Glomerular Filtration Rate Decline in Alport Syndrome.

BACKGROUND: A progressive trajectory toward renal failure is common in patients with Alport syndrome. Genotype-phenotype correlations have been well described; however, the natural history of the trajectory toward renal failure is not well described. OBJECTIVE: The objective of this study is to describe the natural history of renal function decline in a cohort of Alport syndrome patients. DESIGN: Retrospective observational cohort study. SETTING: British Columbia, Canada, chronic renal disease registry 1995-2012. PATIENTS: 37 biopsy proven Alport syndrome or hematuria with family history of Alport syndrome. MEASUREMENTS: Serial estimated glomerular filtration rate (eGFR) Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient's eGFR measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2 /y decline), stable state (0-2 mL/min/1.73 m2 /y decline), and regressors (>2 mL/min/1.73 m2 /y incline). METHODS: In this retrospective observational cohort study, participants were identified through a chronic renal disease registry in British Columbia, Canada, from 1995 to 2012. Inclusion criteria were biopsy proven or hematuria with a family history of Alport syndrome. Individual patients and family group members were studied. Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient's serial estimated glomerular filtration rate (eGFR) measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2/y decline), stable state (0-2 mL/min/1.73 m2/y decline), and regressors (>2 mL/min/1.73 m2/y incline). LIMITATIONS: Histological or genetic evidence of Alport syndrome is not available in all patients. RESULTS: Median follow-up time was 48.2 months of 37 patients (78% male), with a median age of 36 (interquartile range [IQR], 18-47) and a median age of renal replacement therapy commencement (n = 23) of 38 (IQR = 20-52). Renal function changes were found to be heterogeneous overall, intra-individual and within families. Portion of progressors in eGFR 45-60 mL/min/1.73 m2 was 73.7% (SD, 10.3), whereas 23.6% (SD, 11.0) remained stable. Within eGFR 30-45 mL/min/1.73 m2, 45.6% (SD, 7.0) were progressors, whereas 53.4% (SD, 7.4) remained stable. A large portion of eGFR 15-30 mL/min/1.73 m2 patients were stable (54.8%; SD, 8.4), whereas 25.7% (SD, 7.1) progressed and 19.5% (SD, 5.6) regressed. CONCLUSIONS: The renal decline in Alport syndrome patients is heterogeneous which has implications for designing clinical trials of interventions.

MISE EN CONTEXTE: Les patients atteints du syndrome d'Alport voient souvent leur état de santé évoluer vers l'insuffisance rénale. La corrélation entre le génotype et le phénotype est bien établie. Par contre, l'histoire naturelle de la trajectoire menant à l'insuffisance rénale demeure mal connue. OBJECTIFS DE L'ÉTUDE: Le principal objectif de cette étude était de caractériser l'histoire naturelle du déclin de la fonction rénale chez une cohorte de patients atteints du syndrome d'Alport. CADRE ET TYPE D'ÉTUDE: Une étude de cohorte observationnelle rétrospective effectuée entre 1995 et 2012 à partir du registre provincial des maladies rénales chroniques de la Colombie-Britannique, au Canada. PATIENTS: Une cohorte de 37 patients dont le diagnostic avait été confirmé par biopsie ou qui présentaient une hématurie conjointement à un historique familial de syndrome d'Alport. MESURES: Le débit de filtration glomérulaire estimé (DFGe) a été mesuré à plusieurs reprises. La trajectoire du déclin de la fonction rénale a été représentée graphiquement en ajustant une méthode d'interpolation cubique par splines de lissage à la série de mesures du débit de filtration glomérulaire estimé (eGFR) du patient. Plusieurs périodes suivant une trajectoire déterminée ont été indexées, échantillonnées aléatoirement et suivies pendant deux ans afin d'évaluer la proportion de cas de progression de la maladie (>5 mL/min/173m2/année de déclin), de patients stationnaires (0 à 2 mL/min/1,73 m2/année de déclin) et de cas de régression (>2 mL/min/1,73 m2/année de remontée). MÉTHODOLOGIE: Les patients qui ont participé à cette étude de cohorte observationnelle et rétrospective ont été recrutés entre 1995 et 2012 au sein d'un registre des patients souffrant d'insuffisance rénale chronique de la Colombie-Britannique, au Canada. La sélection des participants s'est effectuée sur la base d'un diagnostic posé par biopsie OU d'une hématurie en présence d'un historique familial de syndrome d'Alport. Les patients eux-mêmes, ainsi que des membres de leurs familles respectives ont été observés. La trajectoire du déclin de la fonction rénale a été représentée graphiquement en ajustant une méthode d'interpolation cubique par splines de lissage à la série de mesures du débit de filtration glomérulaire estimé (eGFR) du patient. Plusieurs périodes suivant une trajectoire déterminée ont été indexées, échantillonnées aléatoirement et suivies pendant deux ans afin d'évaluer la proportion de cas de progression de la maladie (>5 mL/min/173m2/année de déclin), de patients stationnaires (0 à 2 mL/min/1,73m2/année de déclin) et de cas de régression (>2 mL/min/1,73m2/année de remontée). LIMITES DE L'ÉTUDE: Les données génétiques ou histologiques nécessaires pour la confirmation du syndrome d'Alport étaient absentes pour certains patients. RÉSULTATS: Le suivi s'est effectué auprès de 37 patients dont 78% étaient des hommes et s'est échelonné sur une période moyenne de 48,2 mois. L'âge médian des participants était de 36 ans (Ecart Interquartile [EI] 18, 47) et l'âge médian où ceux-ci avaient commencé une thérapie de remplacement de la fonction rénale était de 38 ans (EI 20, 52). Les changements dans la fonction rénale se sont avérés hétérogènes tant de façon globale pour l'étude que chez les individus ou au sein de leurs familles. La proportion de progression de la maladie pour les patients présentant des valeurs de eGFR entre 45 et 60 mL/min/1,73m2 était de 73,7% (Écart-type [ÉT]: 10,3) tandis que 23,6% (ÉT: 11,0) sont demeurés stables. Dans le groupe de patients dont les valeurs de eGFR se situaient entre 30 et 45 mL/min/1,73m2, une proportion de 45,6% (ÉT: 7,0) était en progression alors que 53,4% (ÉT: 7,4) sont demeurés stables. Une forte proportion des patients présentant des valeurs de eGFR entre 15 et 30 mL/min/1,73m2 soit 54,8% (ÉT: 8,4) sont demeurés stables, tandis que 25,7% (ÉT: 7,1) étaient en progression et 19,5% (ÉT: 5,6) étaient en régression. CONCLUSIONS: Le déclin de la fonction rénale chez les patients atteints du syndrome d'Alport est hétérogène ce qui entraîne des répercussions sur la façon de concevoir les essais d'intervention cliniques.

A Prospective Study of Renal Transplant Recipients: A Fall in Insulin Secretion Underpins Dysglycemia After Renal Transplantation.

BACKGROUND: Dysglycemia (encompassing impaired glucose tolerance and diabetes mellitus) arising after renal transplantation is common and confers a significant cardiovascular mortality risk. Nonetheless, the pathophysiology of posttransplant dysglycemia is not well described. The aim of this study was to prospectively and comprehensively assess glucose handling in renal transplant recipients from before to 12 months after transplantation to determine the underpinning pathophysiology. MATERIALS AND METHODS: Intravenous and oral glucose tolerance testing was conducted before and at 3 and 12 months posttransplantation. An intravenous glucose tolerance test was also performed on day 7 posttransplantation. We followed up 16 transplant recipients for 3 months and 14 recipients for 12 months. Insulin secretion, resistance and a disposition index (DI (IV)), a measure of ß cell responsiveness in the context of prevailing insulin resistance, were also determined. RESULTS: At 12 months, 50% of renal transplant recipients had dysglycemia. Dysglycemia was associated with a dramatic fall in DI (IV) and this loss in ß cell function was evident as early as 3 months posttransplantation (23.5 pretransplant; 6.4 at 3 months and 12.2 at 12 months posttransplant). Differences in the ß cell response to oral glucose challenge were evident pretransplant in those destined to develop dysglycemia posttransplant (2-hour blood glucose level 5.6 mmol/L versus 6.8 mmol/L; P < 0.01). CONCLUSIONS: Dysglycemia after renal transplantation is common, and the loss of insulin secretion is a major contributor. Subclinical differences in glucose handling are evident pretransplant in those destined to develop dysglycemia potentially heralding a susceptible ß cell which under the stressors associated with transplantation fails.

Dysglycemia after renal transplantation: Definition, pathogenesis, outcomes and implications for management.

New-onset diabetes after transplantation (NODAT) is major complication following renal transplantation. It commonly develops within 3-6 mo post-transplantation. The development of NODAT is associated with significant increase in risk of major cardiovascular events and cardiovascular death. Other dysglycemic states, such as impaired glucose tolerance are also associated with increasing risk of cardiovascular events. The pathogenesis of these dysglycemic states is complex. Older recipient age is a consistent major risk factor and the impact of calcineurin inhibitors and glucocorticoids has been well described. Glucocorticoids likely cause insulin resistance and calcineurin inhibitors likely cause ß-cell toxicity. The impact of transplantation in incretin hormones remains to be clarified. The oral glucose tolerance test remains the best diagnostic test but other tests may be validated as screening tests. Possibly, NODAT can be prevented by administering insulin early in patients identified as high risk for NODAT. Once NODAT has been diagnosed altering immunosuppression may be acceptable, but creates the difficulty of balancing immunological with metabolic risk. With regard to hypoglycemic use, metformin may be the best option. Further research is needed to better understand the pathogenesis, identify high risk patients and to improve management options given the significant increased risk of major cardiovascular events and death.