Desidustat in Anemia due to Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-D).

BACKGROUND: A phase 3 study to assess the efficacy and safety of the desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, against the epoetin alfa for the treatment of anemia in patients with chronic kidney disease (CKD) with dialysis dependency. METHODS: DREAM-D was a phase 3, multicenter, open-label, randomized, active-controlled clinical study conducted across 38 centers in India. A total of 392 patients with clinical diagnosis of anemia due to CKD with dialysis need (Erythrocyte Stimulating Agent [ESA] naïve or prior ESA users) and with baseline hemoglobin levels of 8.0-11.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat oral tablets (thrice a week) or epoetin alfa subcutaneous injection for 24 weeks to maintain a hemoglobin level of 10-12 g/dL. The primary endpoint was to assess the change in the hemoglobin level between the desidustat and the epoetin alfa groups from the baseline to evaluation period week 16-24. The key secondary efficacy endpoint was the number of patients with hemoglobin response. RESULTS: The least square mean (standard error) change in hemoglobin from the baseline to week 16-24 was 0.95 (0.09) g/dL in the desidustat group and 0.80 (0.09) g/dL in the epoetin alfa group (difference: 0.14 [0.14] g/dL; 95% confidence interval: -0.1304, 0.4202), which met the prespecified noninferiority margin. The number of hemoglobin responders was significantly higher in the desidustat group (106 [59.22%]) when compared to the epoetin alfa group (89 [48.37%]) (p = 0.0382). The safety profile of the desidustat oral tablet was comparable with the epoetin alfa injection. There were no new risks or no increased risks seen with the use of desidustat compared to epoetin alfa. CONCLUSION: In this study, desidustat was found to be noninferior to epoetin in the treatment of anemia in CKD patients on dialysis and it was well-tolerated. Clinical Trial Registry Identifier: CTRI/2019/12/022312 (India).

Management strategies and outcomes in renal transplant recipients recovering from COVID-19: A retrospective, multicentre, cohort study.

Background: There is an enormous knowledge gap on management strategies, clinical outcomes, and follow-up after kidney transplantation (KT) in recipients that have recovered from coronavirus disease (COVID-19). Methods: We conducted a multi-center, retrospective analysis in 23 Indian transplant centres between June 26, 2020 to December 1, 2021 on KT recipients who recovered after COVID-19 infections. We analyzed clinical and biopsy-confirmed acute rejection (AR) incidence and used cox-proportional modeling to estimate multivariate-adjusted hazard ratios (HR) for predictors of AR. We also performed competing risk analysis. Additional outcome measures included graft loss, all-cause mortality, waiting time from a positive real-time polymerase test (RT-PCR) to KT, laboratory parameters, and quality of life in follow-up. Findings: Among 372 KT which included 38(10·21%) ABO-incompatible, 12(3·22%) sensitized, 64(17·20%) coexisting donors with COVID-19 history and 20 (5·37%) recipients with residual radiographic abnormalities, the incidence of AR was 34 (9·1%) with 1(0·26%) death censored graft loss, and 4(1·07%) all-cause mortality over a median (interquartile range) follow-up of 241 (106-350) days. In our cox hazard proportional analysis, absence of oxygen requirement during COVID-19 compared to oxygen need [HR = 0·14(0·03-0·59); p-value = 0·0071], and use of thymoglobulin use compared to other induction strategies [HR = 0·17(0·03-0.95); p-value = 0·044] had a lower risk for AR. Degree of Human leukocyte antigen (HLA) DR mismatch had the highest risk of AR [HR = 10.2(1·74-65·83); p-value = 0·011]. With competing risk analysis, with death as a competing event, HLA DR mismatch, and oxygen requirement continued to be associated with AR. Age, gender, obesity, inflammatory markers, dialysis vintage, steroid use, sensitization and ABO-incompatibility have not been associated with a higher risk of AR. The median duration between COVID-19 real time polymerase test negativity to transplant was 88(40-145) days (overall), and ranged from 88(40-137), 65(42-120), 110(49-190), and 127(64-161) days in World Health Organization ordinal scale ≤ 3, 4, 5, and 6-7, respectively. There was no difference in quality of life, tacrolimus levels, blood counts, and mean serum creatinine assessed in patients with a past COVID-19 infection independent of severity. Interpretation: Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19. Funding: Sanofi.

Hemolytic uremic syndrome associated with rhabdomyolysis - Need to look beyond kidneys in hemolytic uremic syndrome.

Hemolytic uremic syndrome, a part of thrombotic microangiopathy, is an important cause of acute kidney injury in children. Hemolytic uremic syndrome primarily targets kidney but extrarenal organ involvement is observed in 20-40% of patients. Extra-renal organ involvement in hemolytic uremic syndrome has been associated with greater disease severity and higher mortality. We describe a 31/2-year-old boy of hemolytic uremic syndrome with rhabdomyolysis, which is a rare extrarenal manifestation of hemolytic uremic syndrome. Unlike central nervous or gastrointestinal system involvement in hemolytic uremic syndrome which manifests clinically, muscle involvement may not and, if present, may worsen the existing acute kidney injury and may worsen disease prognosis. Considering the high morbidity and mortality in acute phase of hemolytic uremic syndrome, prompt evaluation to know the extent of extrarenal organ involvement at the earliest is important for management and prognosis of these patients.

Awareness about kidney and its related function/dysfunction in school going children: A survey from the Central India.

In the absence of a national registry, the exact incidence and burden of chronic kidney disease in children in India is not known. The most common diagnosis for which children are likely to see a pediatric nephrologist is nephrotic syndrome constituting almost 40% of cases. Considering all the renal manifestations in the pediatric age group, we designed simply survey to find out the awareness among school going children about the kidney's function and dysfunction in our Indian scenario. More than 95% of children knew that normally humans have two kidneys. Around 50% of school children on an average were not aware of normal location of their kidneys. About 60%-75% of school going children was unaware of all the functions of a normal kidney. More than half of school children had no idea that even one normal kidney was sufficient to lead a normal life. Again more than half of the participant children were unaware of the basic symptoms of the kidney failure. Around 8%-9% of students reported a positive family history of kidney disease in their family. Pediatric population, especially the school going students should be educated from their early years about the basics of any vital organ like the kidney. Here, in the present study, we found that there is the scope of improvement in making children aware of normal functions of a kidney and the abnormalities that occur when the kidneys are malfunctioning. Early diagnosis will lead to reduced kidney-related morbidity and mortality.

An uncommon cause of rapidly progressive renal failure in a lupus patient: Pauci-immune crescentic glomerulonephritis.

We report a case of systemic lupus erythematosus (SLE) who presented with rapidly progressive renal failure (RPRF) with positive antinuclear antibody (ANA) and anti-double-stranded DNA (dsDNA) antibody and active urinary sediment in the form of microscopic hematuria and proteinuria. Provisional clinical diagnosis of lupus nephritis was made. Renal biopsy showed pauci-immune crescentic glomerulonephritis, the diagnosis of which was supported by positive serum anti-MPO antibody. Renal biopsy in SLE patients can sometimes reveal varied pathological entities such as antinuclear cytoplasmic antibodies (ANCAs) positive vasculitis, as in our case, which modified our treatment protocol. Thus, in a patient with SLE presenting with RPRF with active urinary sediments, ANCA serology, and renal biopsy with immunofluorescence examination should be performed always.

Urinary tract infection due to Fusarium oxysporum in an immunocompetent patient with chronic kidney disease.

Infections due to Fusarium species are collectively referred to as fusariosis. Fusarium oxysporum has been reported to cause keratitis, onychomycosis, skin infections, catheter associated fungemia and has not been described as a cause of urinary tract infection. Here, we present the first case of fusariosis with urinary tract involvement in a 67 year old male, with chronic kidney disease and type 2 diabetes mellitus. This case illustrates the ever increasing spectrum of rare but offending pathogenic fungi. Early diagnosis of infection with a specific pathogen may lead to changes in antifungal therapy and may be critical for an improved outcome.

Is survival enough for quality of life in Sagliker Syndrome-uglifying human face appearances in chronic kidney disease?

BACKGROUND: It is known that secondary hyperparathyroidism (SH) and particularly skeletal changes is a severe condition in chronic kidney disease (CKD). Sagliker syndrome (SS) is a very prominent feature in CKD including uglifying human face appearances, short stature, extremely severe maxillary and mandibulary changes, soft tissues in the mouth, teeth-dental abnormalities, finger tip changes and severe psychological problems. METHODS: In the last 8 years we have confronted 36 extremely incredible SS cases in CKD by performing an international study in Turkey, India, Malaysia, Romania and Egypt. RESULTS: In addition to the uglifying human face appearance, we found extremely severe X-ray and tomographical, pantomographical, histo-pathological changes in the head and whole body. Finally, we compared previous face pictures with recent ones. Just a few years earlier they had been pretty and good-looking young boys and girls. By investigating their history, we understood they had not received proper therapy and were in the late-irreversible period. CONCLUSION: SS is a serious and severe complication of CKD. Late and improper treatment leads to abnormalities throughout skeleton particularly in the skull and face. Changes particularly in children and teens become irreversible-disastrous for appearance and psychological health. Appropriate treatment must begin as early as possible in specialized centers. It is possible that SS patients may survive long-term with dialysis, but with all those particular changes could anyone claim this type of life would continue in an acceptable way without extending their height, correcting all the changes in the skull and face, remodeling new faces and most particularly convincing the patients to deal with all those tragi-dramatic psychological problems?

International study on Sagliker syndrome and uglifying human face appearance in severe and late secondary hyperparathyroidism in chronic kidney disease patients.

OBJECTIVE: It is known that skeletal changes due to secondary hyperparathyroidism (SH) can be severe in chronic kidney disease (CKD). Recently described Sagliker syndrome (SS) is a very striking and prominent feature of SH in CKD, including an uglifying appearance to the face, short stature, extremely severe maxillary and mandibulary changes, soft tissue in the mouth, teeth/dental abnormalities, fingertip changes, knee and scapula deformities, hearing abnormalities, and neurological and, more important, severe psychological problems. DESIGN, SETTING, PATIENTS: In the past 8 years, we have encountered 40 cases of SS in SH and CKD by performing an international study in Turkey, India, Romania, Egypt, Maleysia, Tunis, and China. RESULTS: The medical history of these patients showed that they did not receive proper therapy. Changes, particularly in children and teenagers, become irreversible, which was disastrous for the patients both aesthetically and psychologically. CONCLUSION: Treatment must begin early and be the appropriate treatment given in centers with sophisticated skills. Otherwise, the inability to correct all the changes in the skull and face, to remodel a new face, to extending the height, and, most important, to convince the patients to face the dramatic psychological problems can be catastrophic for those patients.

Post traumatic pituitary apoplexy with contiguous intra cerebral hematoma operated through endonasal route--a case report.

Pituitary apoplexy is a clinical syndrome occurring as a consequence of fulminant expansion of pituitary tumor due to massive infarction, necrosis, and hemorrhage. Its association with head injury is rare and only few reports are available. Shear forces on stalk and arterial vasospasm have been proposed to be the possible reasons. The clinical picture is characterized by sudden onset headache, visual symptoms, multiple cranial nerves involvement, meningismus, altered mental status, and hormonal dysfunction. Transsphenoidal decompression is the standard treatment but suprasellar and widespread extension of hematoma may need intracranial approach. We are reporting a rare association of head injury with pituitary apoplexy, where endonasal surgery proved to be a simple useful approach to evacuate contiguous intra-cerebral hematoma with excision of apoplectic pituitary adenoma.