Suneel M. Udani

Epidemiology of hypertensive kidney disease

The prevalence of hypertension, chronic kidney disease (CKD) and end-stage renal disease (ESRD) attributable to hypertension continues to rise worldwide. Identifying the precise prevalence of CKD attributable to hypertension is difficult owing to the absence of uniform criteria to establish a diagnosis of hypertensive nephropathy. Despite the increasing prevalence of CKD-associated hypertension, awareness of hypertension among individuals with CKD remains suboptimal and rates of blood-pressure control remain poor. Targeted subgroups involved in studies of CKD seem to reach better rates of blood-pressure control, suggesting that this therapeutic goal can be achieved in patients with CKD. Elevated blood-pressure levels are associated with CKD progression. However, the optimal blood-pressure level and pharmacological agent remains unclear. Physicians treating patients with CKD must recognize the importance of maintaining optimal salt and volume balance to achieve blood-pressure goals. Furthermore, agents that modify the renin–angiotensin–aldosterone axis can be an important adjunct to therapy and physicians must monitor expected changes in serum creatinine and electrolyte levels after their administration. Hypertension remains a common factor complicating CKD. Future investigations identifying early signs of hypertension-related CKD, increasing awareness of the effects of hypertension in CKD and determining optimal therapeutic interventions might help reduce the incidence of hypertensive nephropathy.

The use of renal replacement therapy in acute decompensated heart failure.

The worsening of renal function in the context of decompensated heart failure is an increasingly common clinical scenario, dubbed the cardiorenal syndrome. Its development is not completely understood; however, it results from the hemodynamic and neurohumoral alterations that occur in the setting of left ventricular pressure and volume overload with poor cardiac output. Diuretics have been the mainstay of treatment; however, they are often unsuccessful in reversing the vicious cycle of volume overload, worsening cardiac function, and azotemia. Renal replacement therapy (RRT) in the form of isolated or continuous ultrafiltration (UF) with or without a component of solute clearance (hemofiltration or hemodialysis) has been increasingly utilized as a therapeutic tool in this setting. Initial clinical trial data on the use of UF have demonstrated promising cardiac outcomes with regard to fluid removal and symptom relief without worsening renal function. The addition of a component of solute clearance may provide additional benefits in these patients with varying degrees of renal impairment. The exact clinical setting in which the various forms of RRT should be applied as initial or early therapy for acute decompensated heart failure (ADHF) remains unknown. More research examining the use of RRT in ADHF is necessary; however, it appears that the patients with the most severe clinical presentations have the best chance of benefiting from the early application of RRT.

The effects of heart failure on renal function.

Heart-kidney interactions have been increasingly recognized by clinicians and researchers who study and treat heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of concomitant cardiac and renal dysfunction remains unclear; however, evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation.

Do fibrates truly preserve kidney function

Despite the many advances in understanding and treating diabetes mellitus and diabetes-related kidney disease, progression of nephropathy, which ultimately leads to end-stage kidney disease, remains unstoppable. In the FIELD study, Davis et al. assert that long-term fenofibrate treatment in patients with type 2 diabetes mellitus might resolve this problem.

Does renal replacement therapy improve outcome? Controversies in acute kidney injury.

All aspects of current treatment of acute kidney injury (AKI), including renal replacement therapy (RRT), are basically supportive. Emergent RRT is indicated in the management of AKI with refractory pulmonary edema, hyperkalemia or metabolic acidosis, or when uremic symptoms or signs develop. More aggressive practitioners use prophylactic RRT inpatients with sustained anuria, persistent oliguria with progressive azotemia and a probable glomerular filtration rate < 10 ml/min, or to prevent uncontrolled positive fluid balance in patients with AKI. However, this approach to RRT initiation in AKI is largely supported by retrospective analyses rather than prospective clinical trials. The approach to RRT dosing in AKI is more evidence-based. Outcomes in single-center studies of higher intensity versus standard RRT (intermittent and/or continuous) have been in consistent. However, two large multicenter negative randomized trials have shifted the weight of evidence towards suggesting provision of an effectively delivered standard dose of RRT in AKI, rather than seeking to increase RRT intensity.

Chronic kidney disease: Do fibrates truly preserve kidney function?

Despite the many advances in understanding and treating diabetes mellitus and diabetes-related kidney disease, progression of nephropathy, which ultimately leads to end-stage kidney disease, remains unstoppable. In the FIELD study, Davis et al. assert that long-term fenofibrate treatment in patients with type 2 diabetes mellitus might resolve this problem.

Adrenocorticotropic hormone analog use for podocytopathies

Background Adrenocorticotropic hormone is being increasingly studied for treatment of various glomerulopathies, most notably membranous nephropathy. Less data are available regarding its use in idiopathic nephrotic syndrome (INS) secondary to minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). We report here our experience with H.P. Acthar® Gel (repository corticotropin injection) as first-line or subsequent therapy in patients with INS. Methods Data were taken from three patients with MCD and ten patients with FSGS from around the US, who were treated with Acthar Gel as initial or subsequent therapy. Treatment was solely at the discretion of the primary nephrologist without a specific protocol. A complete response (CR) was defined as final urine protein-to-creatinine ratio <500 mg/g and a partial response (PR) as 50% decrease without rise of serum creatinine. Side effects and tolerability were noted. Results All three patients with MCD received Acthar Gel as second-line or later immunosuppressive (IS) therapy and all responded (one CR and two PRs). Two of the ten patients with FSGS received Acthar Gel as first-line IS therapy, while the other eight had failed multiple agents. Four of the ten patients with FSGS had responses, including two CRs and two PRs. The three patients with MCD tolerated therapy well without side effects. Five patients with FSGS tolerated therapy well, while five had various steroid-like side effects, resulting in therapy discontinuation in two patients. Conclusion Acthar Gel is a viable alternative IS agent for treatment of INS in patients intolerant or resistant to conventional therapy. More data are needed to better define its appropriate place.

Compliance with Antibiotic Dosing Guidelines in Critically Ill Patients Receiving Renal Replacement Therapy

Background: Compliance with antibiotic dosing guidelines and achievement of target serum concentrations in patients with infection who are on renal replacement therapy (RRT) is complex, essential for supportive care, and not well studied. Objective: To determine adherence rates to antibiotic dosing guidelines in the setting of RRT in the intensive care unit (ICU). Methods: We conducted a retrospective, single-center, cohort study evaluating antibiotic dosing in all patients in the ICU receiving RRT between July 2007 and June 2009. Appropriate dosing was determined by comparing dose administered with established guidelines. Dosing was denoted as accurate if adjustment occurred prior to the third administered dose or, if appropriate dosing is every 12 hours or more, within 24 hours. We compared rates according to modality of RRT (intermittent hemodialysis [IHD] vs continuous veno-venous hemodialysis [CVVHD]), indication for RRT (acute kidney injury [AKI] vs end-stage renal disease [ESRD]), and presence of a clinical pharmacist on rounds. Results: Adherence rates of 546 patients receiving RRT, with 1761 individual antibiotic prescriptions, were analyzed. Dosing errors were more common in the group receiving CVVHD than in the IHD group (58.1% vs 49.5%; p < 0.001). Frequency of dosing errors did not differ significantly between patients receiving RRT for AKI versus those with ESRD (55.4% vs 51.3%; p = 0.24) or in ICUs with or without a pharmacist on rounds (53.0% vs 54.6%; p = 0.67). Underdosing occurred less frequently with a clinical pharmacist on rounds (18.7% vs 31.3%; p < 0.001). However, in-hospital mortality was not significantly different in underdosed individuals compared with the rest of the cohort (52.3% vs 51.6%; p = 0.92). Conclusions: Antibiotic underdosing is common. Increased awareness of dose adjustment guidelines for CVVHD and having a clinical pharmacist on rounds may improve rates of underdosing.

Cytokine Clearances in Critically Ill Patients on Continuous Renal Replacement Therapy

Background/Aims: We sought to quantify any differences in cytokine clearance between continuous venovenous hemofiltration (CVVH-convective) compared to continuous venovenous hemodialysis (CVVHD-diffusive). Methods: We conducted a 20 patient, multicenter, prospective, open-label randomized trial (CVVH or CVVHD) at continuous renal replacement therapy (CRRT) initiation. Blood, urine, and effluent were collected at 0, 4, 24, and 48 h after initiation of CRRT. Serum electrolytes, cytokines levels, and clearances were measured. Cytokines studies included IL-1β, IL-1RA, IL-6, IL-10, and TNFα. Results: We randomized 20 patients to receive CRRT. After 4 h of CRRT there was no difference in total cytokine levels or change in cytokine concentrations across the 2 groups. With the exception of IL-1 RA, all cytokines levels decreased across patient groups regardless of modality. There was no significant difference in cytokine concentration across CRRT modality for any time point. Conclusion: Within the first 4 h of CRRT initiation, there is no significant difference between cytokine or solute clearance between CVVH and CVVHD.

Do fibrates truly preserve kidney function?: Chronic kidney disease

Despite the many advances in understanding and treating diabetes mellitus and diabetes-related kidney disease, progression of nephropathy, which ultimately leads to end-stage kidney disease, remains unstoppable. In the FIELD study, Davis et al. assert that long-term fenofibrate treatment in patients with type 2 diabetes mellitus might resolve this problem.