Impact of focal segmental glomerulosclerosis over the past decade.

OBJECTIVE: This is a study on the demographics and clinical outcomes including the response to therapy of patients with focal segmental glomerulosclerosis (FSGS) over the past decade. MATERIALS AND METHODS: All histologically proven FSGS cases diagnosed between 2008 and 2018 were analyzed for their clinical, laboratory, and histological characteristics including treatment that could influence the disease progression and renal outcome of these patients. We used the Columbia Classification for FSGS for the renal biopsy. RESULTS: There were two subgroups of FSGS patients; those with nephrotic syndrome and those without nephrotic syndrome. Patients with FSGS with non-nephrotic syndrome had poorer survival rates compared to the nephrotic group. For those without nephrotic syndrome, the indices responsible for progression involved more tubular and blood vessel lesions in addition to glomerular pathology compared to those with nephrotic syndrome. Patients with FSGS with nephrotic syndrome responded to immunosuppressants more favorably compared to the non-nephrotic group, though both groups responded with decreasing proteinuria. The nephrotic group had a better 10-year long-term survival rate of 92 vs. 72% for the non-nephrotic group (log-rank 0.002). The 10-year survival for the whole group of FSGS patients was 64%. CONCLUSION: Our data suggest that in FSGS, one of the significant components of the disease is the vascular and tubular damage, apart from the underlying glomerular pathology, resulting in varying responses to therapy, and the difference is reflected in inherently poorer response to immunosuppressant therapy in those without nephrotic syndrome as opposed to those with nephrotic syndrome, who responded to immunosuppressant therapy (IST) with stabilization of renal function and had less blood vessel and tubular lesions.

The use of medium cutoff dialyzers in patients with multiple myeloma and acute kidney injury requiring hemodialysis: A systematic review.

BACKGROUND: Patients with multiple myeloma and high serum levels of circulating free light chains (FLC) have increased risk of acute kidney injury (AKI) secondary to cast nephropathy and is associated with poor survival. Despite removal of FLC by medium cutoff (MCO) dialyzer, the role of MCO hemodialysis (HD) in the treatment of cast nephropathy and its clinical benefits remain unknown. METHODS: A systematic review was conducted to establish the effectiveness of MCO dialyzer and clinical outcomes, compared to other forms of dialyzers in the removal of FLC, in myeloma patients with AKI. The primary outcome was effectiveness of MCO-HD in reducing serum FLC. The secondary outcomes were HD independence, estimated glomerular filtrate rate, mortality rates, length of hospitalization, rebound of serum FLC before the next dialysis, removal of other molecules during dialysis, and adverse events. RESULTS: We identified three case series, with a total of 17 patients. There were no randomized controlled trials (RCTs) or cohort studies. These case series showed that MCO dialyzer was effective in the removal of FLC and led to a reduction in FLC concentration post-dialysis. The majority of the case series did not have comparator arm and renal and/or other clinical outcomes. CONCLUSION: MCO dialyzer appeared to be effective in the removal of FLC based on the existing limited data. However, more data, particularly large-scale RCTs, are needed to assess the use of MCO dialyzer in reducing serum FLC and its effect on clinical outcomes in patients with multiple myeloma and AKI.

Regional citrate anticoagulation vs systemic heparin anticoagulation for double-filtration plasmapheresis.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) has been utilized for immunomodulation in kidney transplantation. Anticoagulation is important to maintain circuit patency during DFPP. We aimed to compare the efficacy and safety of regional citrate anticoagulation (RCA) with systemic heparin anticoagulation during DFPP in kidney transplant recipients. METHODS: A retrospective cohort study was conducted to compare the efficacy and safety of RCA (RCA-DFPP) to systemic heparin anticoagulation (Hep-DFPP) for DFPP among kidney transplant recipients in a single tertiary center. RESULTS: A total of 112 sessions of DFPP were performed for 23 subjects, of which 62 sessions were RCA-DFPP and 50 sessions were Hep-DFPP. There were 13 sessions (11.6%) of premature circuit clotting, 10 sessions (16.1%) for RCA-DFPP and 3 sessions (6.0%) for Hep-DFPP (P = .10). All premature circuit clotting episodes occurred in subjects who underwent DFPP through a vascular catheter. Premature circuit clotting was associated with the use of a vascular catheter (odds ratio [OR] 14.2, 95% confidence interval [CI] 2.7-73.7; P < .01) and high postfilter ionized calcium (OR 12.7, 95% CI 1.4-112.5; P < .01). There was no major bleeding event. Hep-DFPP was associated with higher occurrence of hypocalcemia (OR 1.1, 95% CI 1.0-1.2; P < .01) and metabolic acidosis (OR 1.4, 95% CI 1.2-2.0; P = .04), while hypomagnesemia was more common for RCA-DFPP (OR 2.9, 95% CI 1.1-7.4; P = .03). CONCLUSION: Amongst kidney transplant patients who receive DFPP therapy, RCA-DFPP may be comparable to Hep-DFPP for the maintenance of circuit patency. Functioning vascular access is vital in avoiding premature clotting of the circuit. Close monitoring of electrolyte imbalances and coagulopathy related to DFPP is recommended.

Regional Citrate Anticoagulation during Double-Filtration Plasmapheresis in Kidney Transplant Recipients: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) may be used for immunomodulation in kidney transplant (KTx). While DFPP reduces plasma product exposure, risk of circuit clotting merits adequate anticoagulation. Regional citrate anticoagulation (RCA) avoids the risks of systemic anticoagulation, but a protocol for RCA-DFPP is not previously widely described. METHODS: We conducted a single-center retrospective cohort study involving adult (≥21 years old) KTx recipients who underwent RCA-DFPP from 2018 to 2020 to investigate efficacy and safety for an RCA protocol during DFPP in KTx recipients. RESULTS: Fifty-one (85%) of 60 RCA-DFPP sessions in 17 patients completed without circuit clotting. Circuit clotting was associated with high post-filter ionized calcium (28 vs. 3.7%, odds ratio 10.1, 95% CI 1.1-89.4, p = 0.037). Hypo- and hypercalcemia developed in 5 (8.3%) and 8 (13.3%) sessions, respectively, but no adverse effects were noted despite severe hypocalcemia in one. There was no significant change in pre- and post-RCA-DFPP sodium, bicarbonate, albumin, and platelet levels. With regards DFPP procedure, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) was observed following 38 (64.4%) and 12 (20.3%) sessions, respectively. Severely prolonged (>1.5 × upper limit normal) PT and aPTT were recorded in 2 sessions each. Expectedly, hypofibrinogenemia developed after 31 (51.7%) sessions: including 4 (6.7%) severe hypofibrinogenemia (<0.5 g/L). Two patients developed bleeding requiring blood product transfusion. The median total volume of fluids administered per session was 1.495 (1.373-1.612) L; post-RCA-DFPP significant weight gain of 0.5 (0-1.25) kg was noted. Diuretic was commenced or dose increased following 20 (33.3%) sessions for fluid balance management. DISCUSSION/CONCLUSION: Protocol-based RCA for DFPP is feasible and safe in KTx recipients. However, DFPP-related coagulopathy can develop consequent to treatment; caution should be exercised for patients with bleeding risk. Close monitoring and management of the patients' electrolytes, especially hypocalcemia and hypomagnesemia, and fluid status is recommended.

Evolution of IgA nephropathy in Singapore over four decades and a comparison of two cohorts from the first and fourth decade.

OBJECTIVE: In this study, we trace the changes in the clinical and histological pattern of IgA nephritis (IgAN) in Singapore as it has evolved over 4 decades and compare the clinical, demographic, histological, and renal outcome of patients with IgAN from the 1st decade and the 4th decade. MATERIALS AND METHODS: This is a retrospective study of all histologically proven IgAN diagnosed between 1976 and 2018. Clinical, laboratory, and histological characteristics between the 1st and the 4th decade, including treatment which could influence the disease progression and renal outcome of these two groups, were compared. We used the Oxford classification to compare the renal biopsy changes for these 2 decades as we were able to retrieve 125 renal biopsy tissues for the 1st cohort of IgAN studied in the 1970s for the comparative study. RESULTS: The commonest clinical presentation throughout the first 3 decades was asymptomatic hematuria and proteinuria (63, 52, and 49%, respectively). In the 4th decade, nephrotic syndrome (31%) was the commonest followed by asymptomatic hematuria and proteinuria (30%), hypertension (21%), and chronic renal failure (11%). The data showed that treatment can modify the Oxford MEST - Crescent scores. Renin-angiotensin system (RAS) blockers modified the S scores, immunosuppressants modified the T and C scores, and combination therapy with RAS blockers and immunosuppressants modified the E, S, and T scores. CONCLUSION: The Oxford MEST classification offers a robust and expressive classification for early and late disease progression with respect to the development of end-stage renal disease (ESRD). E and S seem to be indices of continuing disease activity with progressive glomerulosclerosis, probably still amenable to therapy, but T was a predictive indicator for those destined for ESRD and no longer amenable to therapy.

Description of parallel and sequential configurations for concurrent therapeutic plasma exchange and continuous kidney replacement therapy in adults.

Therapeutic plasma exchange (TPE) and continuous kidney replacement therapy (CKRT) are extracorporeal therapeutic procedures often implemented in management of patients. Critically ill patients may be afflicted with disease processes that require both TPE and CKRT. Performing TPE discontinuous with CKRT is technically easier, however, it disrupts CKRT and may compromise with CKRT efficiency or hemofilter life. Concurrent TPE with CKRT offers several advantages including simultaneous control of disease process and correction of electrolyte, fluid, and acid-base disturbances that may accompany TPE. Additionally, TPE may be performed by either centrifugation method or membrane plasma separation method. The technical specifications of these methods may influence the methodology of concurrent connections. This report describes and reviews two different approaches to circuit arrangements when establishing concurrent TPE and CKRT.

Ensuring Sustainability of Continuous Kidney Replacement Therapy in the Face of Extraordinary Demand: Lessons From the COVID-19 Pandemic.

With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic.

Early Initiation of Renal Replacement Therapy Among Burned Patients With Acute Kidney Injury.

BACKGROUND: Burned patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT) have exceedingly high mortality rates of 73% to 100%. Since January 2011, we have been adopting an early RRT approach in managing burned patients with AKI. Our hypothesis was that early initiation of RRT leads to improved outcome and survival among burned patients with AKI. METHODOLOGY: We conducted a retrospective analysis of Burns Database in Singapore General Hospital from January 2011 to February 2016. Indications for dialysis included serum creatinine of greater than 1.5 times baseline or urine output of less than 0.5 mL/kg per hour for at least 6 consecutive hours. Patients with similar condition from January 2006 to December 2010 were recruited for comparison. RESULT: A total of 27 patients with burns and AKI were recruited from January 2011 to February 2016. The mean age was 45.4 years and 88.9% were male. The mean total burn surface area (TBSA) was 54.8%. The total volume of fluid resuscitation was 2.7 mL/kg per TBSA. The time from onset of burn to RRT was 6.4 days. Most patients presented with stage 1 AKI (51.9%), whereas 22.2% and 25.9% had stage 2 and stage 3 AKI, respectively. Most patients (74.1%) received CRRT and 18.5% received SLED. The mortality rate was 37.0% with majority of death (70%) due to sepsis/multiorgan failure. Only 1 patient required long-term RRT after discharge, and there was no occurrence of abdominal compartment syndrome. The mean age of 15 patients from 2006 to 2010 was 47.8 years. The mean TBSA was 49.5%. Only 26.7% of patients were started on RRT. The mortality rate was 66.7%, which was higher than that of subjects from 2011 to 2016 (37.0%) (P = 0.039). CONCLUSIONS: Optimal timing of RRT for burned patients with AKI has not been established and data on early RRT approach are scarce. The findings of our study suggested that early RRT was associated with lower mortality rates among burned victims with AKI.

Renal outcomes of intensive care burn patients in an Asian tertiary centre.

INTRODUCTION: Acute kidney injury (AKI) is a frequent complication of severe burn injury and is associated with a high mortality rate of up to 80%. We aimed to establish the incidence, mortality rate, and factors related to mortality in adult patients with severe burn injury and AKI with renal replacement therapy (RRT) in Singapore. METHODS: We performed a retrospective cohort study of severely burned patients who were admitted to the Burns Intensive Care Unit (BICU) at the Singapore General Hospital (SGH) from January 2008 to December 2016. We compared patients with AKI with RRT who survived with those who did not survive. As there were changes in the protocol for burns management after 2013, we also compared patients with AKI with RRT who survived with non-survivors in each of the 2008-2012 and 2013-2016 cohorts. RESULTS: Data of 201 patients were studied. The incidence of AKI with RRT use in severe burn injury was 21.9% and their mortality rate was 50.0%. The non-survivors had significantly higher median burned total body surface area (p = 0.043), earlier AKI (p = 0.046), earlier use of RRT (p = 0.035), lower rate of renal recovery (p = <0.0001), higher rates of adult respiratory distress syndrome (ARDS) (p = 0.005) and shock with vasopressors (p = 0.009) compared to the survivors. The survival rate was 36.8% in the 2008-2012 cohort, but improved to 60.0% in the 2013-2016 cohort. In the 2008-2012 cohort, the non-survivors developed AKI earlier (day 0 admission vs. day 3 admission, p = 0.039), and were initiated on RRT at lower serum creatinine level (173.5 µmol/L vs. 254.0 µmol/L, p = 0.042), when compared to the survivors in this same cohort. On the other hand, there were no significant differences in the renal status and fluid balance parameters between the non-survivors and survivors in the 2013-2016 cohort. CONCLUSIONS: The incidence of AKI with RRT in the Singapore study cohort was high, but their mortality rate was relatively lower compared to other study cohorts. Severity of AKI and use of RRT were associated with poor prognosis. Large scale study is required to further study the risk factors for mortality in this group of patients and establish cause-and-effect relationship.

A prospective study of clinical characteristics and outcomes of acute kidney injury in a tertiary care Centre.

BACKGROUND: Acute kidney injury (AKI) is a major global health problem. We aim to evaluate the epidemiology, risk factors and outcomes of AKI episodes in our single centre. METHODOLOGY: We prospectively identified 422 AKI and acute on chronic kidney disease episodes in 404 patients meeting KDIGO definitions using electronic medical records and clinical data from 15th July to 22nd October 2016, excluding patients with baseline estimated GFR (eGFR) of < 15 mL/min. Patients were followed up till 6 months after AKI diagnosis. RESULTS: The mean age was 65.8 ± 14.1. Majority of patients were male (58.2%) of Chinese ethnicity (68.8%). One hundred and thirty-two patients (32.6%) were diagnosed in acute care units. Seventy-five percent of patients developed AKI during admission in a non-Renal specialty. Mean baseline eGFR was 50.2 ± 27.7 mL/min. Mean creatinine at AKI diagnosis was 297 ± 161 µmol/L. Renal consultations were initiated at KDIGO Stages 1, 2 and 3 in 58.9, 24.5 and 16.6% of patients, respectively. Three hundred and ten (76.7%) patients had a single etiology of AKI with the 3 most common etiologies of AKI being pre-renal (27.7%), sepsis-associated (25.5%) and ischemic acute tubular necrosis (15.3%). One hundred and nine (27%) patients received acute renal replacement therapy. In-hospital mortality was 20.3%. Six-month mortality post-AKI event was 9.4%. On survival analysis, patients with KDIGO Stage 3 AKI had significantly shorter survival than other stages. CONCLUSION: AKI is associated with significant in-hospital to 6-month mortality. This signifies the pressing need for AKI prevention, early detection and intervention in mitigating reversible risk factors in order to optimize clinical outcomes.

Augmented Adsorptive Blood Purification during Continuous Veno-Venous Haemodiafiltration in a Severe Septic, Acute Kidney Injury Patient: Use of oXiris®: A Single Centre Case Report.

The use of the oXiris® haemofilter during continuous veno-venous haemodiafiltration (CVVHDF) for acute kidney injury (AKI) and severe sepsis is not completely understood. Although this filter has in vitro adsorptive properties for blood-borne cytokines and other humoural mediators of sepsis, its clinical usefulness is uncertain. Given its inherent adsorptive limitation for septic mediators, we developed a CVVHDF protocol in which the oXiris haemofilter was electively changed every 12 h even though there was no clotting or adverse circuit pressures. Augmented filter membrane adsorption was conducted for 3 consecutive days. We treated a critically ill patient with severe sepsis secondary to a gram-negative bacterial infection and sepsis-associated acute kidney injury (SA- AKI) in this way. The patient required high-dose vasopressor support, required mechanical ventilation, had received 12 h of CVVHDF with conventional M100 haemofilter, was on broad spectrum antibiotics and other conventional intensive care unit (ICU) care, prior to institution of the frequent oXiris haemofilter change protocol. Following the start of elective 12 hourly oXiris filter change, the patient showed reduction in the need for vasopressor and by Day 4 of this SA- AKI frequent filter change protocol, vasopressor requirement ceased, he was extubated. He survived ICU and but not hospital stay. To this end, more clinical studies are needed.

Hypophosphatemia in critically ill patients with acute kidney injury treated with hemodialysis is associated with adverse events.

Background. Hypophosphatemia in critically ill patients may be exacerbated by renal replacement therapy (RRT). We aimed to identify risk factors and adverse outcomes associated with hypophosphatemia in intensive care patients treated with RRT for acute kidney injury (AKI). Methods. This was a secondary analysis of data from a single-center prospective cohort study of medical and surgical intensive care patients with RRT for AKI between 18 December 2010 and 3 April 2013. Demographic, comorbidity, laboratory and RRT data were retrieved from patient case notes and electronic medical records. Outcomes assessed were hypophosphatemia (serum phosphate <0.94 mmol/L) during RRT, intensive care unit (ICU) mortality, and duration of mechanical ventilation and vasopressor support. Results. Among 96 patients who received acute RRT, 25 (26.0%) developed hypophosphatemia. On multivariate logistic regression, serum phosphate at RRT initiation [adjusted odds ratio (OR) 0.29, 95% confidence interval (CI) (0.09, 0.91), P = 0.03] was independently associated with hypophosphatemia during acute RRT. Patients with hypophosphatemia during RRT required longer ventilatory support [median 12 (interquartile range: 8, 17) days versus 5 (3, 9) days, P < 0.001] and vasopressor support [5 (4, 15) days versus 2 (2, 6) days, P = 0.003] compared with those without hypophosphatemia but there was no significant difference in ICU mortality [5 patients (20.0%) versus 24 patients (33.8%), P = 0.20]. Hypophosphatemia during RRT was independently associated with prolonged mechanical ventilation (≥7 days) [adjusted OR 14.0, 95% CI (1.37, 143.90), P = 0.03]. Conclusion. Hypophosphatemia is common during acute RRT for critically ill patients and was associated with adverse clinical outcomes.

30-year follow-up study of IgA nephritis in a Southeast Asian population: an evaluation of the Oxford histological classification
.

BACKGROUND: In 1985 we reported that 11% of a cohort of 151 patients with IgA nephritis (IgAN) had developed end-stage renal disease (ESRD) after a follow-up period of 5 years. 15 years later, 35% had developed ESRD. METHODS: We retrieved 125 stored renal biopsy paraffin blocks of the original cohort. From these, 102 patients were included in the present study and scored according to the Oxford classification as 21 specimens with less than 8 glomeruli were excluded and in 2 others, tissue samples were too tiny for a re-block. ESRD was ascertained by linking the study cohort to the Singapore Renal Registry at the National Registry of Diseases Office. RESULTS: Renal survival curves for each of the Oxford MEST lesions: endocapillary proliferation (E) (p < 0.04), segmental glomerulosclerosis (S) (p < 0.05), tubular atrophy/interstitial fibrosis (p < 0.0001) were significantly associated with ESRD. Mesangial hypercellularity, less commonly associated with progressive chronic kidney disease (CKD) in the study, was independently associated with ESRD at 30 years (p < 0.03). In this cohort, E and S were associated with lower eGFR at presentation and doubling of serum creatinine in the first 5 years. This study's initial 5 years was representative of the "natural history" of IgAN since no renin-angiotensin system (RAS) blockers or immunosuppression were administered. This represents the early phase of disease progression. E and S may be considered "early disease activity predictors". CONCLUSION: Mesangial hypercellularity and tubular atrophy/interstitial fibrosis (M1 and T1/T2 lesion) of the Oxford classification independently predicted long term ESRD.
.

Long-Term Risk of Progressive Chronic Kidney Disease in Patients with Severe Acute Kidney Injury Requiring Dialysis after Coronary Artery Bypass Surgery.

AIM: Few studies have evaluated patients after cardiac surgery for subsequent chronic kidney disease (CKD) which increases cardiovascular morbidity and mortality. This study aimed to ascertain the long-term renal outcome in adult patients with severe acute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery. METHODS: This is a single-center retrospective cohort study of consecutive adult patients who received acute dialysis for AKI after CABG between February 8, 2009 and January 30, 2011. Data on pre- and intra-operative factors were retrieved from electronic medical records. The primary endpoint was CKD progression as defined by dialysis dependence or doubling of serum creatinine from the pre-operative level. Secondary endpoints included in-hospital mortality and renal function at 3 months and 1 year. RESULTS: Fifty-five patients required acute dialysis after CABG. The median age was 67 years (IQR: 61, 75), and 70.9% were male. Median pre-operative serum creatinine was 157 µmol/l (IQR: 122, 203). A total of 19 patients (34.5%) died. The median follow-up time for hospital survivors was 44.2 months (IQR: 25.0, 49.4) after surgery. Among the 36 survivors, 14 patients (38.9%) reached the primary endpoint. Patients with CKD progression had higher pre-operative serum creatinine [median 214 µmol/l (IQR: 159, 399) vs. 155 µmol/l (112, 187), p = 0.015] and lower eGFR [median 20.4 ml/min/1.73 m(2) (IQR: 11.9, 38.2) vs. 39.9 ml/min/1.73 m(2) (25.9, 55.5), p = 0.027] compared to those who did not have CKD progression. CONCLUSION: Patients with severe AKI after CABG are at high risk of long-term renal dysfunction and should be monitored regularly for deterioration.

Initiating acute dialysis at earlier Acute Kidney Injury Network stage in critically ill patients without traditional indications does not improve outcome: a prospective cohort study.

AIM: Optimal timing for acute renal replacement therapy (ARRT) initiation in critically ill patients with acute kidney injury (AKI) is unclear. We aimed to evaluate outcomes in patients who initiated ARRT for traditional indications versus those who met Acute Kidney Injury Network (AKIN) criteria without traditional indications. METHODS: This was a single-centre prospective cohort study of medical and surgical intensive care patients with AKI. Traditional indications for ARRT initiation included: serum potassium ≥6.0 mmol/L, serum urea ≥30 mmol/L, arterial pH < 7.25, serum bicarbonate <10 mmol/L, acute pulmonary oedema, acute uraemic encephalopathy or pericarditis. In absence of these indications, ARRT was commenced if patients had (i) AKIN Stage 3 or (ii) AKIN Stage 1 or 2 with 'compelling' conditions. Primary outcomes were intensive care unit (ICU) and in-hospital mortality. RESULTS: ARRT was initiated in 140 patients: traditional indications in 56 (40%); AKIN Stage 3 without traditional indications in 38 (27%); and AKIN Stage 1 or 2 with 'compelling' conditions in 46 (33%) patients. Traditional indications at ARRT initiation was associated with increased in-hospital mortality (adjusted odds ratio (95% confidence interval), 6.48 (1.54, 27.29)). In absence of traditional indications, earlier ARRT initiation, as defined by those with AKIN Stage 1 or 2, did not decrease ICU deaths (30.0% vs 18.8%, P = 0.30) or in-hospital mortality (50.0% vs 34.2%, P = 0.15) compared with those who were started on ARRT for AKIN Stage 3. CONCLUSIONS: Presence of traditional indications at ARRT initiation was associated with greater mortality. Initiating dialysis at earlier AKIN stage did not improve survival in patients without traditional indications.

The significance of tubular and glomerular proteinuria in critically ill patients with severe acute kidney injury.

OBJECTIVE: Critically ill patients with acute kidney injury (AKI) frequently need acute renal replacement therapy (aRRT). We evaluated an inexpensive, rapid quantitative and qualitative analysis of proteinuria on the course of AKI patients requiring aRRT in intensive care. METHOD: This was a prospective, observational study of critically ill patients with severe established AKI or Acute on Chronic Kidney Injury (AoCKI) requiring aRRT. Urine samples were analyzed using Sodium-Dodecyl-Sulphate-Polyacryamide Gel Electrophoresis (SDS-PAGE). RESULTS: A total of 30 critically ill patients were studied. Those who died have higher APACHE II (29 ± 6 vs. 20 ± 5, p<0.001), multi-organ failure (0.7 ± 0.5 vs. 0.2 ± 0.4, p < 0.02) and Tubular/Glomerular ratio (114 ± 60 vs. 75± 37, p < 0.05).The renal non-recoverers have higher baseline creatinine (415 ± 328 vs. 125± 19 umol/l, p < 0.01), urinary Dipstick value (1.8±0.8 vs. 0.5±0, p <0.05) and Glomerular score (3.0 ± 1.8 vs. 0.6 ± 0.2, p < 0.02).Heavy tubular proteinuria also predicts a longer duration of interim dialysis support and mortality whereas glomerular proteinuria correlates with development of chronicity and End Stage Renal Disease (ESRD). CONCLUSIONS: The dominant presence of tubular proteinuria is associated with poor survival in patients who have high APACHE II score and multi-organ failure. It also correlates with a longer duration of dialysis support in survivals. Renal Non-recoverers had heavy dominant presence of glomerular proteinuria. SDS-PAGE proteinuria analysis offers a reliable and inexpensive method to prognosticate proteinuria in this group of critically ill patients.

Genomics and disease progression in IgA nephritis.

Apart from clinical, histological and biochemical indices, genomics are now being employed to unravel the pathogenetic mechanisms in the disease progression of IgA nephritis (IgAN). The results of angiotensin converting enzyme (ACE) gene polymorphism have been controversial. Those patients with the DD genotype seem to have a poorer prognosis. However, with high dose angiotensin receptor blocker (ARB) therapy, the ACE gene polymorphism status of a patient may no longer be a matter for concern as those with the DD genotype would also respond favourably to high dose ARB therapy. Association studies with gene sequencing and haplotypes have suggested that multiple genes are involved in the pathogenesis of IgAN. Some workers have reported a synergistic effect in the combined analysis of AGT-M235T and ACE I/D polymorphism. With the use of deoxyribo nucleic acid (DNA) microarray, tens of thousands of gene expressions genome-wide can be examined together simultaneously. A locus of familial IgAN has been described with strong evidence of linkage to IgAN1 on chromosome 6q22-23. Two other loci were reported at 4q26-31 and 17q12-22. DNA microarray techniques could also help in the identification of specific pathogenic genes that are up- or down-regulated and this may allow genome wide analyses of these genes and their role in the pathogenesis and progression of IgAN. Recently, using genome-wide association studies (GWAS) more loci for disease susceptibility for IgAN have been identified at 17p13, 8p23, 22q12, 1q32 and 6p21.

National Health Survey on the prevalence of urinary abnormalities in the population: then and now (1975 to 2012).

INTRODUCTION: This paper presents the results of a community survey on urinary abnormalities which covered 1/80th of the population of Singapore in 1975. These findings were compared with the data from the Singapore National Service Registrants in 1974 as well as data from a recent survey in Singapore and that of other Asian and Western countries. MATERIALS AND METHODS: The study covered 18,000 persons aged 15 years and above, representing a sampling fraction of 1/80th of the population. A total of 16,808 respondents attended the field examination centres, of whom 16,497 had their urine sample tested representing 92.7% of the sample population. RESULTS: In the dipstick urine testing at the field examination centres, 769 subjects (4.6%) were found to have urinary abnormalities. Two hundred and eighty-two (36.7%) of these 769 subjects were found to have urinary abnormalities based on urine microscopy constituting a prevalence of 1.71%. The prevalence of proteinuria was 0.63% and for both haematuria and proteinuria was 0.73%. The prevalence for hypertension was 0.43% and renal insufficiency was 0.1%. DISCUSSION: The consensus is that routine screening for chronic kidney disease (CKD) in the general population is not cost effective as the yield is too low. Whilst, most studies showed that screening of the general population was not cost effective, it has been suggested that screening for targeted groups of subjects could help to identify certain risk groups who may benefit from early intervention to prevent or retard the progression of CKD. CONCLUSION: The prevalence of urinary abnormalities in Singapore has remained the same, now and three decades ago.