Severe lupus pneumonitis: A case of life-saving multimodal therapy with rituximab and corticosteroids.

Severe lupus pneumonitis is a rare and life-threatening complication of systemic lupus erythematosus (SLE), characterized by its rapid progression and high mortality rate. This case report describes the clinical trajectory and therapeutic management of a young Aboriginal female with established lupus nephritis who developed severe lupus pneumonitis. Despite her stable renal condition under long-term immunosuppressive treatment, she experienced acute respiratory distress, leading to her admission to the intensive care unit and subsequent mechanical ventilation. The diagnostic process was complicated by the difficulty in obtaining tissue biopsies, necessitating reliance on clinical judgement and radiological evidence to formulate a diagnosis. The patient was treated with pulsed intravenous methylprednisolone followed by rituximab infusions, resulting in significant clinical and radiological improvement. This case highlights the importance of early and intensive immunosuppressive therapy in the management of severe lupus pneumonitis and underscores the utility of a multidisciplinary approach in overcoming diagnostic ambiguities. Furthermore, it contributes to the growing body of evidence supporting the efficacy of rituximab in severe lupus pneumonitis cases, offering insights into potential therapeutic avenues when conventional management strategies are inadequate or unsuitable.

Outcomes in organ transplants from donors with melanoma: a systematic review.

Melanoma transmitted through organ transplantation is an increasingly reported event. Immunosuppression increases the risk of melanoma; however, transmission of malignancy from transplanted organs is a distinct etiology of melanoma occurrence. The risk of transmission of melanoma from an organ donor with melanoma has yet to be determined. The authors aimed to investigate this phenomenon by reviewing the outcomes of patients that received organs from donors with melanoma. A systematic literature review was conducted with emphasis on identifying organ donors with known histories of melanoma and reported information regarding recipients of their organs. The databases PubMed, MEDLINE, Embase, and JBI EBP were searched in January 2023. Search terms included "melanoma," terms for solid organs, "donor," "transplant," "transmission," and their variations as well as terms related to temporal relations. Inclusion criteria were articles that stated outcomes in organ recipients from donors that had a diagnosis of melanoma either pretransplant or postmortem. Reference lists of selected articles were hand searched for further studies. A total of 232 articles were identified from the search parameters. After applying inclusion and exclusion criteria, 13 articles were selected. Hand searching the references of these articles yielded four additional articles. Of the 75 organ recipients that received organs from donors with known melanoma, 43 developed melanoma. While a definitive quantitative risk cannot be ascertained based on our review, the numerous reported cases of melanoma in organ recipients from donors that have melanoma should still be considered by clinicians.

Factors associated with functional arteriovenous fistula at hemodialysis start and arteriovenous fistula non-use in a single-center cohort.

BACKGROUND: The gold standard of commencing hemodialysis with a functional arteriovenous fistula (AVF) is challenging. We aim to review factors associated with functional AVF at hemodialysis start at a tertiary hospital. METHODS: We retrospectively reviewed incident hemodialysis patients or who had AVF creation at a single tertiary hospital from 2011 to 2016. Data was extracted for patient comorbidities, duration from referral to AVF creation and hemodialysis start, estimated glomerular filtration rate (eGFR) at surgical referral, referring nephrologist, events accelerating eGFR decline, and revisions for "failing to mature" AVF to assess factors associated with non-functioning AVF or late AVF creation, using multinomial logistic regression. RESULTS: Two hundred two patients received hemodialysis and 51 had AVF creation but did not dialyze (AVF futility rate 20%). Of these, 133 (66%) commenced hemodialysis with a central venous catheter (CVC) and 69 (34%) with an AVF. Patients with functional AVFs at hemodialysis start were referred earlier than those with non-functional AVFs (median 256 vs 66 days before hemodialysis start, p = 0.001). Age, sex, eGFR at surgical referral, and comorbidities were not predictive of patients with functional AVFs. Events accelerating eGFR decline were associated with an increased incidence of CVC at hemodialysis start (risk ratio (RR) 4.21, 95% confidence interval (CI) 1.96-9.03, p < 0.0001). Referring nephrologists external to our renal unit may be associated with non-functional AVF at hemodialysis start (RR 6.60, 95% CI 1.74-25.13, p = 0.006). CONCLUSIONS: We found that functional AVFs required referral a median of 256 days prior to hemodialysis start and events accelerating eGFR decline increase the incidence of CVC at hemodialysis start. Age, sex, eGFR at surgical referral, and comorbidities did not inform the likelihood of timely AVF creation and evaluation of further predictive pre-dialysis factors is necessary to identify patients requiring early AVF creation whilst minimizing the cost of unnecessary procedures.

Double partial nephrectomy in allograft transplanted kidney.

A 61-year-old female presented with an incidental anterior mid pole renal mass on ultrasound. She had previously undergone live directed donor renal transplantation 13 years prior. As the 10 year survival of living transplant recipients increases, malignancy presentations will continue to rise. Nephron sparing surgery in renal allografts is sparse due to difficult operative dissection and complicated hila vascular control. We present the use of manual atraumatic graded bowel clamp pressure around the resected tumour as a viable option to safely perform partial nephrectomy in a transplanted kidney.

Femoral Neck X-Ray Absorptiometry Parameters and Peripheral Quantitative Computer Tomography Tibial Cortical Density Predict Survival in Dialysis Patients.

BACKGROUND: Low bone mineral density (BMD) is a known independent predictor of mortality in the general elderly population. However, studies in patients with end-stage renal disease (ESRD) are limited. The present study evaluated mortality during long-term follow-up in a population of patients having dialysis for ESRD, in whom BMD was also measured. METHODS: Fifty-eight patients with ESRD were recruited consecutively from a dialysis clinic and followed prospectively for 6 years. Baseline BMD of the lumbar spine and femoral neck (FN) were measured by X-ray absorptiometry and by peripheral quantitative CT at the radius and tibia. Serum calcium, phosphate, parathyroid hormone (PTH), and albumin were measured at baseline. RESULTS: During follow-up, 25 patients died. Univariate analysis showed that mortality was significantly associated with FN-BMD: hazards ratio (HR) per 0.1 g/cm2 decrease 1.50 (95% CI 1.07-2.10), p = 0.019; FN-T score: HR per 1-SD decrease 1.84 (95% CI 1.16-2.92), p = 0.009; and tibial cortical density: HR per 10 mg/cm3 decrease 1.08 (95% CI 1.02-1.14), p = 0.010. In multivariate analysis with stepwise adjustment for age, sex, transplant status, albumin, PTH, phosphate, dialysis duration, diabetes, and smoking, FN-T score remained significantly associated with mortality: HR per 1-SD decrease 1.82 (95% CI 1.02-3.24), p = 0.044, whereas the HR for FN-BMD and tibial cortical density were no longer significant. When 4 patients who had peritoneal dialysis were excluded, the HR relating FN-BMD, FN-T score, and tibial cortical density to mortality remained significant but became insignificant when albumin was included in the multivariate analysis. CONCLUSION: Reduced FN-BMD, FN-T score, and tibial cortical density were significantly associated with an increased risk of death in patients with ESRD.

Renal fibrosis is the common feature of autosomal dominant tubulointerstitial kidney diseases caused by mutations in mucin 1 or uromodulin.

For decades, ill-defined autosomal dominant renal diseases have been reported, which originate from tubular cells and lead to tubular atrophy and interstitial fibrosis. These diseases are clinically indistinguishable, but caused by mutations in at least four different genes: UMOD, HNF1B, REN, and, as recently described, MUC1. Affected family members show renal fibrosis in the biopsy and gradually declining renal function, with renal failure usually occurring between the third and sixth decade of life. Here we describe 10 families and define eligibility criteria to consider this type of inherited disease, as well as propose a practicable approach for diagnosis. In contrast to what the frequently used term 'Medullary Cystic Kidney Disease' implies, development of (medullary) cysts is neither an early nor a typical feature, as determined by MRI. In addition to Sanger and gene panel sequencing of the four genes, we established SNaPshot minisequencing for the predescribed cytosine duplication within a distinct repeat region of MUC1 causing a frameshift. A mutation was found in 7 of 9 families (3 in UMOD and 4 in MUC1), with one indeterminate (UMOD p.T62P). On the basis of clinical and pathological characteristics we propose the term 'Autosomal Dominant Tubulointerstitial Kidney Disease' as an improved terminology. This should enhance recognition and correct diagnosis of affected individuals, facilitate genetic counseling, and stimulate research into the underlying pathophysiology.

Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1.

BACKGROUND AND OBJECTIVES: The genetic cause of medullary cystic kidney disease type 1 was recently identified as a cytosine insertion in the variable number of tandem repeat region of MUC1 encoding mucoprotein-1 (MUC1), a protein that is present in skin, breast, and lung tissue, the gastrointestinal tract, and the distal tubules of the kidney. The purpose of this investigation was to analyze the clinical characteristics of families and individuals with this mutation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Families with autosomal dominant interstitial kidney disease were referred for genetic analysis over a 14-year period. Families without UMOD or REN mutations prospectively underwent genotyping for the presence of the MUC1 mutation. Clinical characteristics were retrospectively evaluated in individuals with the MUC1 mutation and historically affected individuals (persons who were both related to genetically affected individuals in such a way that ensured that they could be genetically affected and had a history of CKD stage IV or kidney failure resulting in death, dialysis, or transplantation). RESULTS: Twenty-four families were identified with the MUC1 mutation. Of 186 family members undergoing MUC1 mutational analysis, the mutation was identified in 95 individuals, 91 individuals did not have the mutation, and111 individuals were identified as historically affected. Individuals with the MUC1 mutation suffered from chronic kidney failure with a widely variable age of onset of end stage kidney disease ranging from 16 to >80 years. Urinalyses revealed minimal protein and no blood. Ultrasounds of 35 individuals showed no medullary cysts. There were no clinical manifestations of the MUC1 mutation detected in the breasts, skin, respiratory system, or gastrointestinal tract. CONCLUSION: MUC1 mutation results in progressive chronic kidney failure with a bland urinary sediment. The age of onset of end stage kidney disease is highly variable, suggesting that gene-gene or gene-environment interactions contribute to phenotypic variability.

Differential regulation of Snail by hypoxia and hyperglycemia in human proximal tubule cells.

The centrality of the transcriptional regulator Snail in epithelial-to-mesenchymal transformation (EMT), known to occur in models of diabetic nephropathy, has not been established. Transforming growth factor beta-1 (TGFbeta1) is induced in diabetic nephropathy and induces both Snail and EMT. Hypoxia inducible factors (HIFs) are known to induce Snail, independent of TGFbeta1. Notch induction is integral to Snail induction and EMT in tumour cells, but its role in the kidney is unknown. The present study was undertaken to determine the upstream regulators of Snail in the kidney in high glucose and hypoxic conditions. HK-2 cells were cultured in normoxic, hypoxic, high glucose and combined hypoxic/high glucose conditions. The expression of HIF1alpha, NotchIC, Snail, Lysyl oxidase-like 2 (Loxl2), and Hairy and Enhancer Split-1 (Hes1) were measured. We found that hypoxia increased HIF1alpha expression; however, concurrent exposure to high glucose blunted this effect. A similar pattern was observed in Lox12 expression, suggesting that Loxl2 was downstream of HIF1alpha, which was confirmed using siRNA techniques. Snail was upregulated by hypoxia and high glucose and in combination the effect was additive, suggesting independent upstream activation pathways by the two stimuli. Hes1 was upregulated by high glucose and to a lesser extent by hypoxia, but the effect of the combined stimuli was no greater than that observed with high glucose alone. NotchIC was downregulated by both hypoxia and high glucose, and in combination the effect was additive. Therefore, this study suggests that hypoxia and high glucose induce Snail expression through distinct pathways, independent of Notch signalling.

Blood pressure is a major risk factor for renal death: an analysis of 560 352 participants from the Asia-Pacific region.

Chronic kidney disease is a major worldwide public health problem that causes substantial morbidity and mortality. Studies from the Asia-Pacific region have reported some of the highest chronic kidney disease prevalence rates in the world, but access to dialysis is limited in many countries, making it imperative to identify high-risk individuals. We performed a participant-level data overview of prospective studies conducted in the Asia-Pacific region to quantify the magnitude and direction of the associations between putative risk factors and renal death. Age- and sex-adjusted Cox proportional hazards models were applied to pooled data from 35 studies to calculate hazard ratios (95% CIs) for renal death associated with a standardized change in risk factors. Among 560 352 participants followed for a median of 6.8 years, a total of 420 renal deaths were observed. Continuous and positive associations among systolic blood pressure, diastolic blood pressure, fasting blood glucose, and total cholesterol levels with renal death were observed, as well as a continuous but inverse association with high-density lipoprotein cholesterol. Systolic blood pressure was the strongest risk factor for renal death with each SD increase in systolic blood pressure (19 mm Hg) associated with >80% higher risk (hazard ratio: 1.84; 95% CI: 1.60 to 2.12). Neither cigarette smoking nor excess weight was related to the risk of renal death (P>0.10). The results were similar for cohorts in Asia and Australia. These results suggest that primary prevention strategies for renal disease should focus on individuals with elevated blood pressure, diabetes mellitus, and dyslipidemia.

A method for the isolation of glomerular and tubulointerstitial endothelial cells and a comparison of characteristics with the human umbilical vein endothelial cell model.

BACKGROUND: Abnormalities in the structure and function of glomerular endothelial cells play a pivotal role in the development of progressive renal disease. The vascular abnormalities observed in the renal tubulointerstitium, however, correlate more strongly with progressive renal failure. Therefore, the successful isolation and culture of human renal microvascular endothelial cells from both the glomerulus and tubulointerstitium are paramount in studying renal disease models. METHODS AND RESULTS: This study describes a simple and reproducible method for the isolation of human tubulointerstitial and glomerular endothelial cells by using immunomagnetic separation with anti-platelet endothelial-cell adhesion (anti-PECAM-1) Dyna beads, followed by manual weeding of mesangial and fibroblast contamination. No significant changes in morphological or immunohistochemical characteristics were observed up to passage two of culture. The in vitro characteristics of the endothelial cells were compared to the renal cortical endothelial cells in vivo and the standard human umbilical vein endothelial cell model (HUVECs). Similar to HUVECs, both populations of renal microvascular endothelial cells had a classical cobblestone appearance, stained positively for von Willebrand Factor and PECAM-1 and negatively for antifibroblast surface antigen and anticytokeratin. Differences in the expression of von Willebrand Factor, Wiebel Palade bodies and Flk-1 staining were observed between glomerular and tubulointerstitial endothelial cells. These immunohistochemical characteristics suggested that tubulointerstital endothelial cells were more closely aligned to HUVECS than to the glomerular endothelial cells. This observation indicated that HUVECs may be a suitable model for determining the tubulointerstitial endothelial response to systemic injury. CONCLUSION: In conclusion, a unique and novel method for the differential isolation of both glomerular and tubulointerstitial endothelial cells has been developed. Significantly, characterization of these populations suggests a role for HUVECS in the study of renal tubulointerstitial disease.