Effect of Renin-Angiotensin-Aldosterone System Blockers on Adverse Outcomes in COVID-19 Patients.

INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) of the renin-angiotensin-aldosterone system (RAAS) serves as a functional receptor to gain entry into the cells for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). The interaction between SARS-CoV-2 and ACE2 is a potential virulent factor in infectivity. Our study aimed to ascertain the association of RAAS inhibitors with adverse cardiovascular and other outcomes in hospitalized COVID-19 patients. METHODS: This is a retrospective study of medical records of ≥18-year-old patients hospitalized for COVID-19 from March 2020 to October 2020. Primary outcomes were acute cardiovascular events (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction type 1, acute congestive heart failure, acute stroke) and mortality. Secondary outcomes were respiratory failure, need for and duration of mechanical ventilation, acute deep vein thrombosis or pulmonary embolism (DVT/PE), and readmission rate. RESULTS: Among 376 hospitalized COVID-19 patients, 149 were on RAAS inhibitors. No statistically significant differences were found between RAAS inhibitor and non-RAAS inhibitor groups with respect to acute cardiovascular events (6% vs. 6.2%, p = 0.94), acute DVT/PE (4.7% vs. 4.8%, p = 0.97), hypoxia (62.4% vs. 58.6%, p = 0.46), need for mechanical ventilation (18.1% vs. 16.7%, p = 0.72), mortality (19.5% vs. 22%, p = 0.56), and readmission rate (11.4% vs. 14.1%, p = 0.45). Some nuances discovered were a higher rate of hospitalizations among Native Americans receiving RAAS inhibitors (30.2% vs. 19.8%) and significantly lower levels of procalcitonin in patients on RAAS inhibitors. CONCLUSIONS: Among hospitalized patients with COVID-19, those on RAAS inhibitors showed no significant differences in acute cardiovascular events, acute DVT/PE, hypoxia, need for mechanical ventilation, readmission, or mortality rate compared to those not on them. However, further large-scale studies are needed to validate these findings.

An update on LDL apheresis for nephrotic syndrome.

Low-density lipoprotein (LDL) apheresis has been used increasingly in clinical practice for the treatment of renal diseases with nephrotic syndrome (NS), specifically focal segmental glomerulosclerosis (FSGS). Persistent hyperlipidemia for prolonged periods is nephrotoxic and leads to chronic progressive glomerular and tubulointerstitial injury. Effective management of hyperlipidemia with HMG-CoA reductase inhibitors or LDL apheresis in drug-resistant NS patients may prevent the progression of renal disease and, in some patients, resolution of NS symptoms. Available literature reveals beneficial effects of LDL apheresis for NS refractory to drug therapy. Here we update on the current understanding of lipid nephrotoxicity and application of LDL apheresis to prevent progression of renal diseases.

Pediatric intradialytic hypotension: recommendations from the Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup.

Intradialytic hypotension (IDH) is a common adverse event resulting in premature interruption of hemodialysis, and consequently, inadequate fluid and solute removal. IDH occurs in response to the reduction in blood volume during ultrafiltration and subsequent poor compensatory mechanisms due to abnormal cardiac function or autonomic or baroreceptor failure. Pediatric patients are inherently at risk for IDH due to the added difficulty of determining and attaining an accurate dry weight. While frequent blood pressure monitoring, dialysate sodium profiling, ultrafiltration-guided blood volume monitoring, dialysate cooling, hemodiafiltration, and intradialytic mannitol and midodrine have been used to prevent IDH, they have not been extensively studied in pediatric population. Lack of large-scale studies on IDH in children makes it difficult to develop evidence-based management guidelines. Here, we aim to review IDH preventative strategies in the pediatric population and outlay recommendations from the Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup. Without strong evidence in the literature, our recommendations from the expert panel reflect expert opinion and serve as a valuable guide.

Renal replacement therapy in the management of intoxications in children: recommendations from the Pediatric Continuous Renal Replacement Therapy (PCRRT) workgroup.

BACKGROUND: Intentional or unintentional ingestions among children and adolescents are common. There are a number of ingestions amenable to renal replacement therapy (RRT). METHODS: We systematically searched PubMed/Medline, Embase, and Cochrane databases for literature regarding drugs/intoxicants and treatment with RRT in pediatric populations. Two experts from the PCRRT (Pediatric Continuous Renal Replacement Therapy) workgroup assessed titles, abstracts, and full-text articles for extraction of data. The data from the literature search was shared with the PCRRT workgroup and two expert toxicologists, and expert panel recommendations were developed. RESULTS AND CONCLUSIONS: We have presented the recommendations concerning the use of RRTs for treatment of intoxications with toxic alcohols, lithium, vancomycin, theophylline, barbiturates, metformin, carbamazepine, methotrexate, phenytoin, acetaminophen, salicylates, valproic acid, and aminoglycosides.

Endothelin-1 as a therapeutic target in autosomal dominant polycystic kidney disease
.

AIMS: Endothelin-1 (ET-1) is associated with the pathophysiology of autosomal dominant polycystic kidney disease (ADPKD) via cyst progression. Elevated concentrations of ET-1 in ADPKD correlate with many phenotypic changes in the kidney such as renal cyst development, interstitial fibrosis, and glomerulosclerosis. In addition, an imbalance between renal ETA and ETB receptors possibly leads to more severe disease progression. The objective of this review is to determine whether evaluating the efficacy of these drugs in treatment of cystic kidney disease may be a worthwhile aim, as determined by results from animal and human models. MATERIALS AND METHODS: PubMed/Medline, Embase, and Google Scholar databases were searched using the key words "endothelin, endothelin-1 antagonists, and autosomal dominant polycystic kidney disease". All animal and human studies describing the effects of endothelin and endothelin-1 antagonists in ADPKD subjects were included in the review. RESULTS: Urinary ET-1 concentrations could serve as a noninvasive surrogate biomarker for kidney ET-1 levels, as it is inversely associated with eGFR, independent of age, sex, and blood pressure. Elevated urinary excretion of ET-1 may be a biomarker for early renal injury. Antagonization of ET-1 may hopefully be a novel therapy for slowing progression of kidney damage in ADPKD. CONCLUSION: Based on the literature reviewed in this manuscript, it is proposed that further research evaluating the efficacy of endothelin antagonists in treatment of cystic kidney disease is warranted. More human studies need to be performed with larger sample sizes. Therefore, the recommendation for treatment is inconclusive at this time.
.

Role of Lipoprotein Apheresis in Cardiovascular Disease Risk Reduction.

BACKGROUND AND AIM: Elevated low-density lipoprotein cholesterol and/or lipoprotein(a) are established risk factors for cardiovascular disease (CVD). Management of hypercholesterolemia consists of drug therapies, including statins and proprotein convertase subtilisin/kexin type 9 inhibitors. In patients with familial hypercholesterolemia (FH), lipoprotein apheresis (LA) is utilized to control lipid levels. However, LA is not currently a standard therapy for non-FH. This review summarizes the literature regarding LA therapy in CVD prevention. METHODS: PubMed/MEDLINE databases were searched using the keywords "LA" and "CVD". Citations were individually reviewed for relevance. RESULTS: The efficacy of LA was clearly demonstrated, largely based on evidence from observational studies. In patients who are unresponsive to traditional lipid-lowering medications, LA effectively reduced serum lipoprotein levels and adverse cardiovascular events. CONCLUSION: It was concluded that LA is a safe and effective technique that could be considered in the management of hypercholesterolemia and future risk. Randomized control trials would further support a role for LA as a therapeutic option.

Hemodialysis in neonates and infants: A systematic review.

Hemodialysis (HD) in neonates and infants poses unique challenges due to high risks of mortality attributable to obligatory small blood flow volumes. Although HD is often necessary in neonates, its effectiveness and feasibility are poorly understood. The aim of this review is to describe in detail the few studies reporting on HD in neonates and infants (<12 months old) and then dissertate more broadly on the subject with an emphasis on recent innovations with potential to overcome traditional barriers for effective HD in this population. We detail the clinical characteristics, outcomes, technical considerations, maintenance and complications associated with HD, and provide guidance for addressing challenges associated with HD in this population.

The use of eculizumab in gemcitabine induced thrombotic microangiopathy.

BACKGROUND: Thrombotic microangiopathy (TMA) secondary to gemcitabine therapy (GiTMA) is a very rare pathology that carries a poor prognosis, with nearly half of the cases progressing to end stage renal disease. GiTMA is most commonly associated with adenocarcinomas, most notably pancreatic cancers. The mainstay of management is withdrawal of the offending drug and supportive care. Plasmapheresis has a limited role and hemodialysis may help in the management of fluid overload secondary to renal failure. Furthermore, a C5 inhibitor, eculizumab, has been successfully used in the treatment of GiTMA. CASE PRESENTATION: A 64-year-old Caucasian female with history of pancreatic adenocarcinoma on gemcitabine chemotherapy presented with signs and symptoms of fluid overload and was found to have abnormal kidney function. Her BP was 195/110 mmHg, serum creatinine 4.48 mg/dl, hemoglobin 8.2 g/dl, platelets 53 × 103/cmm, lactate dehydrogenase 540 IU/L, and was found to have schistocytes on blood film. A diagnosis of TMA secondary to gemcitabine therapy was suspected. Hemodialysis for volume overload and daily plasmapheresis were initiated. After six days of plasmapheresis, renal function did not improve. Further work up revealed ADAMTS 13 activity >15%, low C3, and stool culture and Shiga-toxin PCR were negative. Renal biopsy was consistent with TMA. Gemcitabine was discontinued, but renal function failed to improve and eculizumab therapy was considered due to suspicion of aHUS. Serum creatinine >2.26 mg/dl and a platelet count of >/= 30 × 109/L is highly suggestive of aHUS, while TTP is more likely when creatinine is <2.26 mg/dl and platelet count of <30 × 109/L. She received intravenous eculizumab for eight months, which resulted in significant improvement of renal function. Other markers of hemolysis, namely LDH and bilirubin, also rapidly improved following eculizumab therapy. Plasmapheresis and hemodialysis were discontinued after two and eight weeks of initiation respectively. CONCLUSION: Chemotherapy induced TMA is very rare and requires a high index of clinical suspicion for timely diagnosis. Discontinuation of the offending drug and supportive care is the main stay of treatment; however, eculizumab has been shown to be beneficial in GiTMA. Further research is required to validate this approach.

Hematopoietic stem cell transplantation and acute kidney injury in children: A comprehensive review.

AKI in the setting of HSCT is commonly investigated among adult patients. In the same way, malignancies requiring treatment with HSCT are not limited to the adult patient population, AKI following HSCT is frequently encountered within pediatric patient populations. However, inadequate information regarding epidemiology and pathophysiology specific to pediatric patients prevents development of appropriate and successful therapeutic strategies for those afflicted. Addressing AKI in the context of sinusoidal obstruction syndrome, chemotherapy, thrombotic microangiopathy and hypertension post chemotherapy, glomerulonephritis, and graft versus host disease provides greater insight into renal impairment associated with these HSCT-related ailments. To obtain a better understanding of AKI among pediatric patients receiving HSCT, we investigated the current literature specifically addressing these areas of concern.

Effect of Aspirin Use on the Adverse Outcomes in Patients Hospitalized for COVID-19.

Background: Coronavirus disease 2019 (COVID-19) triggers multiple components of the immune system and causes inflammation of endothelial walls across vascular beds, resulting in respiratory failure, arterial and venous thrombosis, myocardial injury, and multi-organ failure leading to death. Early in the COVID-19 pandemic, aspirin was suggested for the treatment of symptomatic individuals, given its analgesic, antipyretic, anti-inflammatory, anti-thrombotic, and antiviral effects. This study aimed to evaluate the association of aspirin use with various clinical outcomes in patients hospitalized for COVID-19. Methods: This was a retrospective study involving patients aged ≥ 18 years and hospitalized for COVID-19 from March 2020 to October 2020. Primary outcomes were acute cardiovascular events (ST elevation myocardial infarction (STEMI), type 1 non-ST elevation myocardial infarction (NSTEMI), acute congestive heart failure (CHF), and acute stroke) and death. Secondary outcomes were respiratory failure, need for mechanical ventilation, and acute deep vein thrombosis (DVT)/pulmonary embolism (PE). Results: Of 376 patients hospitalized for COVID-19, 128 were taking aspirin. Significant proportions of native Americans were hospitalized for COVID-19 in both aspirin (22.7%) and non-aspirin (24.6%) groups. Between aspirin and non-aspirin groups, no significant differences were found with regard to mechanical ventilator support (21.1% vs. 15.3%, P = 0.16), acute cardiovascular events (7.8% vs. 5.2%, P = 0.32), acute DVT/PE (3.9% vs. 5.2%, P = 0.9), readmission rate (13.3% vs. 12.9%, P = 0.91) and mortality (23.4% vs. 20.2%, P = 0.5); however, the median duration of mechanical ventilation was significantly shorter (7 vs. 9 days, P = 0.04) and median length of hospitalization was significantly longer (5.5 vs. 4 days, P = 0.01) in aspirin group compared to non-aspirin group. Conclusion: No significant differences were found in acute cardiovascular events, acute DVT/PE, mechanical ventilator support, and mortality rate between hospitalized COVID-19 patients who were taking aspirin compared to those not taking aspirin. However, larger studies are required to confirm our findings.

Impact of Chronic Conditions, Healthcare Utilization, and Demographics on Advance Care Planning.

Context: Unraveling the intricacies of what factors influence advance care planning (ACP) is an ongoing research challenge. Research shows much ACP is crisis-based and takes place at the end of life. Complicating this late-stage approach may be demographic differences based on race, ethnicity and socioeconomic status. Objective: We examined the relationship between demographic factors, chronic health conditions, and healthcare utilization in predicting who was most likely to engage in ACP activities, including designating a durable power of attorney for healthcare (DPOAHC), having a living will, and discussing wishes with family or others. Methods: We conducted a secondary analysis using 2018 Health and Retirement Study (HRS) exit data provided by a proxy for the deceased participant that matched the 2016 survey participant data (N = 884). Generalized linear mixed models were used for the analysis. Results: The number of chronic health conditions and healthcare utilization were not associated with ACP activities, but several of the demographic variables showed strong associations. Participants who were female, white, older, and from a higher socioeconomic status were more likely to have engaged in ACP. Conclusion: People continue to defer ACP discussions and documentation end of life or when facing medical crises. More needs to be done to reach out to younger adults, racial minorities, and those with lower socioeconomic status to encourage them to engage in ACP.

The Role of Endothelin and Endothelin Antagonists in Chronic Kidney Disease.

BACKGROUND: Endothelins (ET) are a family of peptides that act as potent vasoconstrictors and pro-fibrotic growth factors. ET-1 is integral to renal and cardiovascular pathophysiology and exerts effects via autocrine, paracrine and endocrine signaling pathways tied to regulation of aldosterone, catecholamines, and angiotensin. In the kidney, ET-1 is critical to maintaining renal perfusion and controls glomerular arteriole tone and hemodynamics. It is hypothesized that ET-1 influences the progression of chronic kidney disease (CKD), and the objective of this review is to discuss the pathophysiology, and role of ET and endothelin receptor antagonists (ERAs) in CKD. SUMMARY: The use of ERAs in hypertensive nephropathy has the potential to decrease proteinuria, and in diabetic nephropathy has the potential to restore glycocalyx thickness, also decreasing proteinuria. Focal segmental glomerular sclerosis has no specific Food and Drug Administration-approved therapy currently, however, ERAs show promise in decreasing proteinuria and slowing tissue damage. ET-1 is a potential biomarker for autosomal dominant polycystic kidney disease progression and so it is thought that ERAs may be of some therapeutic benefit. KEY MESSAGES: Multiple studies have shown the utility of ERAs in CKD. These agents have shown to reduce blood pressure, proteinuria, and arterial stiffness. However, more clinical trials are needed, and the results of active or recently concluded studies are eagerly awaited.

An Overview of Rickets in Children.

Rickets is a common bone disease worldwide that is associated with disturbances in calcium and phosphate homeostasis and can lead to short stature and joint deformities. Rickets can be diagnosed based on history and physical examination, radiological features, and biochemical tests. It can be classified into 2 major groups based on phosphate or calcium levels: phosphopenic and calcipenic. Knowledge of categorization of the type of rickets is essential for prompt diagnosis and proper management. Nutritional rickets is a preventable disease through adequate intake of vitamin D through both dietary and sunlight exposure. There are other subtypes of rickets, such as vitamin D-dependent type 1 rickets and vitamin D-dependent type 2 rickets (due to defects in vitamin D metabolism), renal rickets (due to poor kidney function), and hypophosphatemic rickets (vitamin D-resistant rickets secondary to renal phosphate wasting wherein fibroblast growth factor-23 (FGF-23) often plays a major role), which requires closer monitoring and supplementation with activated vitamin D with or without phosphate supplements. An important development has been the introduction of burosumab, a human monoclonal antibody to FGF-23, which is approved for the treatment of X-linked hypophosphatemia among children 1 year and older.

Association of pulse pressure, pulse pressure index, and ambulatory arterial stiffness index with kidney function in a cross-sectional pediatric chronic kidney disease cohort from the CKiD study.

The morbidity and mortality of adult and pediatric chronic kidney disease (CKD) and end-stage renal disease (ESRD) populations are mainly driven by cardiovascular disease (CVD). Improving CVD outcomes focuses on risk assessment of factors including diastolic blood pressure (DBP), systolic blood pressure (SBP), left ventricular mass index (LVMI), pulse pressure (PP), and pulse pressure index (PPi), which is calculated as PP/SBP. These markers are also proven predictors of CKD progression; however, their role in children has not been established. This study aims to evaluate the relationship between PP, PPi, ambulatory arterial stiffness index (AASI), and proteinuria with kidney function in pediatric CKD patients; it is a retrospective analysis of 620 patients (1-16 years) from the NIDDK Chronic Kidney Disease in Children (CKiD) registry. The authors analyzed data for three separate cohorts: an overall CKD as well as immunological versus non-immunological cause for CKD groups. An inverse relationship was found between SBP, DBP, and PP with iGFR and LVMI in the overall CKD group. Our immunological CKD subgroup showed significantly higher serum creatinine, SBP, DBP, and PP values with significantly lower serum albumin levels compared to the non-immunological group. There were no significant differences with iohexol-based glomerular filtration rate (iGFR), LVMI, PPi, or high-sensitivity C-reactive protein (hs-CRP) between the two groups. A subgroup analysis demonstrated that SBP, DBP, and PP all correlated significantly with LVMI in the immunological CKD patients but not the non-immunological subgroup. Additionally, AASI data in the overall CKD population were significantly correlated with PP, PPi, and DBP. This study is one of the first to correlate noninvasive measurements of vascular compliance including PP, PPi, and AASI with iGFR and LVMI in a pediatric CKD cohort. Improving our understanding of surrogate markers for early CVD is integral to improving the care of pediatric CKD population as these patients have yet to develop the hard end points of ESRD, heart failure, myocardial infarction, or stroke.

Consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy.

Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the ammonia concentrations and presenting symptoms of the patient, is crucial. This expert Consensus Statement presents recommendations for the management of hyperammonaemia requiring KRT in paediatric populations. Additional studies are required to strengthen these recommendations.

Atypical Hemolytic-Uremic Syndrome: An Update on Pathophysiology, Diagnosis, and Treatment.

Atypical hemolytic uremic syndrome (aHUS), a rare variant of thrombotic microangiopathy, is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. The condition is associated with poor clinical outcomes with high morbidity and mortality. Atypical HUS predominantly affects the kidneys but has the potential to cause multi-organ system dysfunction. This uncommon disorder is caused by a genetic abnormality in the complement alternative pathway resulting in over-activation of the complement system and formation of microvascular thrombi. Abnormalities of the complement pathway may be in the form of mutations in key complement genes or autoantibodies against specific complement factors. We discuss the pathophysiology, clinical manifestations, diagnosis, complications, and management of aHUS. We also review the efficacy and safety of the novel therapeutic agent, eculizumab, in aHUS, pregnancy-associated aHUS, and aHUS in renal transplant patients.

Dermatologic manifestations in end stage renal disease.

Skin manifestations are commonly seen in end stage renal disease (ESRD). Skin involvement in this population can be extensive and dramatically worsen quality of life. Close observation of the skin and nails of ESRD patients by clinicians allows for timely diagnosis and treatment, which ultimately improves quality of life and reduces mortality. In this article we focus on the cutaneous changes most commonly seen in ESRD patients. PubMed/Medline database search was done for published literature on skin manifestations in ESRD patients. All the available literature was reviewed and relevant articles were used to discuss about clinical features, pathogenesis, histology and treatment of each skin disorder in ESRD patients. Most commonly encountered skin manifestations in patients with ESRD are pruritus, xerosis, pigmentation changes, nail changes, perforating disorders, calcifying disorders, bullous dermatoses and nephrogenic systemic fibrosis. Skin manifestations in ESRD can be difficult to treat and multiple comorbidities in this patient population can exacerbate these disorders. Many of the treatment options are experimental with evidence largely derived from the case reports and small clinical trials. More large-scale trials are needed to firmly establish evidence based treatment guidelines. Prompt evaluation and management of these disorders improve morbidity and quality of life in ESRD patients.

Overview of Monogenic or Mendelian Forms of Hypertension.

Monogenic or Mendelian forms of hypertension are described as a group of conditions characterized by insults to the normal regulation of blood pressure by the kidney and adrenal gland. These alterations stem from single mutations that lead to maladaptive overabsorption of electrolytes with fluid shift into the vasculature, and consequent hypertension. Knowledge of these various conditions is essential in diagnosing pediatric or early-onset adult hypertension as they directly affect treatment strategies. Precise diagnosis with specific treatment regimens aimed at the underlying physiologic derangement can restore normotension and prevent the severe sequelae of chronic hypertension.

Dextran-Sulfate Plasma Adsorption Lipoprotein Apheresis in Drug Resistant Primary Focal Segmental Glomerulosclerosis Patients: Results From a Prospective, Multicenter, Single-Arm Intervention Study.

Background: Focal segmental glomerulosclerosis (FSGS) causes end stage renal disease (ESRD) in significant proportion of patients worldwide. Primary FSGS carries poor prognosis and management of FSGS patients, refractory to standard treatments or resistant to steroids, remains a major challenge. Lipoprotein apheresis is a therapeutic approach for drug resistant primary FSGS and post-renal transplant primary FSGS recurrence. Objectives: To examine the safety and probable benefit at 1, 3, 6, 12, and 24-months following completion of apheresis treatment using Liposorber® LA-15 system in patients with nephrotic syndrome (NS), due to refractory primary FSGS or primary FSGS associated NS, in post renal transplant children. Material and Methods: Prospective, multicenter, single-arm intervention study using Liposorber® LA-15 system. Patients ≤21 years old with drug resistant or drug intolerant NS secondary to primary FSGS with glomerular filtration rate (GFR) ≥60 ml/min/1.73 m2 or post renal transplant patients ≤21 years old with primary FSGS associated NS were included in the study. Each patient had 12 dextran-sulfate plasma adsorption lipoprotein apheresis sessions over a period of 9 weeks. All patients were followed up at 1, 3, 6, 12, and 24-months following completion of treatment. Results: Of 17 patients enrolled, six were excluded from the outcome analysis (protocol deviations). Of the remaining 11 patients, all but one have completed apheresis treatments. Three patients were lost to follow-up immediately after completion of apheresis and excluded from outcome analysis. At one-month follow-up, 1 of 7 patients (14.3%) attained partial remission of NS while 2 of 4 subjects (50%) and 2 of 3 subjects (66.7%) had partial/complete remission at 3- and 6-months follow-up, respectively. One of two patients followed up for 12 months had complete remission and one patient had partial remission of NS after 24 months. Improved or stable eGFR was noted in all patients over the follow-up period. Conclusion: The results of our multicenter study showed improvement in the response rates to steroid or immunosuppressive therapy and induced complete or partial remission of proteinuria in some of the patients with drug resistant primary FSGS. The main limitation of our study is the small number of subjects and high dropout rate.

Management of pain in end-stage renal disease patients: Short review.

Pain management in end stage renal disease (ESRD) patients is a complex and challenging task to accomplish, and effective pain and symptom control improves quality of life. Pain is prevalent in more than 50% of hemodialysis patients and up to 75% of these patients are treated ineffectively due to its poor recognition by providers. A good history for PQRST factors and intensity assessment using visual analog scale are the initial steps in the management of pain followed by involvement of palliative care, patient and family counseling, discussion of treatment options, and correction of reversible causes. First line should be conservative management such as exercise, massage, heat/cold therapy, acupuncture, meditation, distraction, music therapy, and cognitive behavioral therapy. Analgesics are introduced according to WHO guidelines (by the mouth, by the clock, by the ladder, for the individual, and attention to detail) using three-step analgesic ladder model. Neuropathic pain can be controlled by gabapentin and pregabalin. Substitution/addition of opioid analgesics are indicated if pain control is not optimal. Commonly used opioids in ESRD patients are tramadol, oxycodone, hydromorphone, fentanyl, methadone, and buprenorphine. Methadone, fentanyl, and buprenorphine are the ideal analgesics in ESRD. However, complex pain syndrome requires multidrug analgesic regimen comprising opioids, non-opioids, and adjuvant medication, which should be individualized to the patient to achieve adequate pain control.