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Acute kidney injury (AKI) is an abrupt reduction in kidney function caused by different pathological processes. It is associated with a significant morbidity and mortality in the acute phase and an increased risk of developing End Stage Renal Disease. Despite the progress in the management of the disease, mortality rates in the last five decades remain unchanged at around 50%. Therefore there is an urgent need to find new therapeutic strategies to treat AKI. Lysosomal proteases, particularly Cathepsin D (CtsD), play multiple roles in apoptosis however, their role in AKI is still unknown. Here we describe a novel role for CtsD in AKI. CtsD expression was upregulated in damaged tubular cells in nephrotoxic and ischemia reperfusion (IRI) induced AKI. CtsD inhibition using Pepstatin A led to an improvement in kidney function, a reduction in apoptosis and a decrease in tubular cell damage in kidneys with nephrotoxic or IRI induced AKI. Pepstatin A treatment slowed interstitial fibrosis progression following IRI induced AKI. Renal transplant biopsies with acute tubular necrosis demonstrated high levels of CtsD in damaged tubular cells. These results support a role for CtsD in apoptosis during AKI opening new avenues for the treatment of AKI by targeting lysosomal proteases.

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The increasing use of extended criteria organs to meet the demand for kidney transplantation raises an important question of how the severity of early ischaemic injury influences long-term outcomes. Significant acute ischaemic kidney injury is associated with delayed graft function, increased immune-associated events and, ultimately, earlier deterioration of graft function. A comprehensive understanding of immediate molecular events that ensue post-ischaemia and their potential long-term consequences are key to the discovery of novel therapeutic targets. Acute ischaemic injury primarily affects tubular structure and function. Depending on the severity and persistence of the insult, this may resolve completely, leading to restoration of normal function, or be sustained, resulting in persistent renal impairment and progressive functional loss. Long-term effects of acute renal ischaemia are mediated by several mechanisms including hypoxia, HIF-1 activation, endothelial dysfunction leading to vascular rarefaction, sustained pro-inflammatory stimuli involving innate and adaptive immune responses, failure of tubular cells to recover and epigenetic changes. This review describes the biological relevance and interaction of these mechanisms based on currently available evidence.

The NF-κB family of transcription factors is important for many cellular functions, in particular initiation and propagation of inflammatory and immune responses. However, recent data has suggested that different subunits of the NF-κB family can suppress the inflammatory response. NF-κB1, from the locus nfκb1, can inhibit transcription, acting as a brake to the recognised pro-inflammatory activity of other NF-κB subunits. We tested the function of NF-κB1 in an acute (nephrotoxic serum (NTS) nephritis) and a chronic (unilateral ureteric obstruction (UUO)) model of renal injury using NF-κB1 (nfκb1−/−) knockout mice. Deficiency in NF-κB1 increased the severity of glomerular injury in NTS-induced nephritis and was associated with greater proteinuria and persistent pro-inflammatory gene expression. Induction of disease in bone marrow chimeric mice demonstrated that the absence of NF-κB1 in either bone marrow or glomerular cells increased the severity of injury. Early after UUO (day 3) there was more severe histological injury in the nfκb1−/− mice but by day 10, disease severity was equivalent in wild type and nfκb1−/− mice. In conclusion, NF-κB1 modifies acute inflammatory renal injury but does not influence chronic fibrotic injury.

Background: Pediatric kidney transplantation was only introduced in Indonesia in 2013. We therefore aimed to assess the characteristics and outcomes of transplants performed from its inception to January 2019. Method: The study had a dual-center retrospective design. We examined the records of kidney transplant recipients and then calculated patient and graft survival rates by Kaplan-Meier survival analysis with 95% confidence intervals (95% CI). Results: In total, 12 kidney transplantations were performed in eleven children during the study period; among these, ten were boys, and nine had renal failure caused by congenital anomaly of the kidney or urinary tract. All donors were living, and all recipients were on dialysis at the time of transplantation, when their median age was 14.5 years (range, 8-19 years). Three patients died of infection in the first year of follow-up and two lost their allograft by the time of their last follow-up (median, 13 months; range, 4-69 months). The 1-year patient survival rate was therefore 68.18% (95% CI, 29.72%-88.61%), which remained unchanged at 3 and 5 years. However, the non-death-censored graft survival rates at 1, 3, and 5 years were 68.18% (95% CI, 29.72%-88.61%), 51.14% (95% CI, 14.5%-79.46%), and 25.57% (95% CI, 1.38%-64.78%), respectively. Conclusion: Patient and graft survival rates after pediatric kidney transplantation in Indonesia are lower than those reported in other countries. Closer patient follow-up and stricter adherence to guidelines could improve transplant outcomes, but we must seek to improve the balance between infection and rejection.

Ectopic scrotum (ES) is a particularly rare congenital malformation of the scrotum and commonly associated with other congenital malformations. A 2-year-old boy was presented with ectopic scrotum, low lesion imperforate anus, spina bifida and pubic diastasis since birth. There are various surgical methods available to be discussed in the management of ES. We performed correction of the ectopic scrotum and concomitant bilateral orchidopexy in one stage of surgery. This procedure is relatively simpler to perform and gives out favorable cosmetic result.

Diagnostic and therapeutic strategies of prostate cancer may largely influenced by patients' age at presentation. This study is aimed to evaluate the characteristics, diagnostic and treatment strategies in prostate cancer patients in our centres. A cross-sectional analytic study of prostate cancer data in two main referral cancer centres, Cipto Mangunkusumo General Hospital and Dharmais National Cancer Centre from 1995-2010, was therefore performed. Patients were divided into 2 sub-populations; below 60 years (younger patients) and 75 years old and above (older patients). PSA levels, diagnostic modalities, Gleason score and therapeutic options were analysed for both and compared using bivariate analysis. 152 patients were <60 years and 210 were ≥75 years. There was no statistical difference in mean PSA level (797.9ng/mL vs 345.3 ng/mL, respectively; p>0.05) and diagnosis was made by biopsy in majority of patients in both groups (68.2% and 71.6% in younger and older groups respectively). Most presented with an advanced disease stage (65.1% and 66.0%, respectively) and there was no statistically significant difference in mean Gleason scores f (8.1 vs 7.7; p>0.05). Primary androgen deprivation therapy (PADT) was the main treatment for overall patients (48.0% and 50.7%, respectively). Radiotherapy and radical prostatectomy are the main therapeutic modalities for younger patients with local and locally advanced disease (39.6% and 35.4% respectively), while the majority of older patients with the same disease stage were treated with radiotherapy and PADT (45.8% and 39.0% respectively). Differences observed in treatment modalities were statistically significant (p<0.0003). We conclude that there is no difference in disease clinical aggressiveness of the two groups but significant differences were obseved in therapeutic strategies utilised with younger and older patients.