Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT.

BACKGROUND: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear. METHODS: In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR). RESULTS: About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar. CONCLUSIONS: Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.

Nephrotoxicity induced by intravitreal vascular endothelial growth factor inhibitors: emerging evidence.

Vascular endothelial growth factor (VEGF) inhibitors have emerged as powerful tools to treat malignant neoplasms and ocular diseases by virtue of their ability to inhibit angiogenesis. Recent data indicate that intravitreal injections of VEGF inhibitors can lead to significant systemic absorption as well as a measurable reduction of plasma VEGF activity. There is increasing evidence showing that vitreal absorption of these drugs is associated with cases of accelerated hypertension, worsening proteinuria, glomerular disease, thrombotic microangiopathy, and possible chronic renal function decline. In this review, the 3 most commonly used anti-VEGF agents-bevacizumab, ranibizumab, and aflibercept-are discussed, highlighting their intravitreal absorption and associated effects on the kidney as a target organ system. We provide clinical suggestions for clinicians to both better manage patients receiving anti-VEGF agents intravitreally and detect any putative systemic renal effects of these agents. While acknowledging the risks of aberrant retinal angiogenesis, it is important for clinicians to be aware of the potential for adverse renal risks with use of these agents.

New Agents in Treatment of Hyperkalemia: an Opportunity to Optimize Use of RAAS Inhibitors for Blood Pressure Control and Organ Protection in Patients with Chronic Kidney Disease.

PURPOSE OF REVIEW: The overactive renin-angiotensin-aldosterone system (RAAS) plays an important part in many pathologic conditions including hypertension, heart failure, and renal disease. Hyperkalemia, a potentially life-threatening side effect of RAAS inhibitors, limits their use. The recent introduction of new hyperkalemia treatments provides opportunities to take full benefit of RAAS inhibitors. RECENT FINDINGS: Optimizing RAAS inhibition is an important therapeutic goal, particularly in chronic kidney disease. Different strategies have been investigated to achieve this goal, including inhibiting the pathway at multiple steps and using maximum or even supramaximal doses. Hyperkalemia is one of the most significant barriers to all of the strategies mentioned above. Up until the recent past, there have been limited therapeutic options available for the prevention and treatment of hyperkalemia in the long term. New promising agents to treat hyperkalemia in outpatient settings, namely, patiromer and sodium zirconium, may provide a solution. This article will review the benefits and risks of RAAS inhibitors, strategies to optimize their use, and the new hyperkalemia treatments that can lower the risk associated with RAAS inhibiting therapies.

Association of Coping Styles with Quality of Life in Cancer Patients.

BACKGROUNDS AND AIM: Cancer patients experience a high level of stress caused by the disease and treatment processes. Dealing with cancer using more beneficial coping styles can effectively improve the quality of life (QOL) and reduce the side effects of cancer, and it is treatment. In this study, we aimed to investigate the relationship between coping styles and QOL in cancer patients. METHODS: The study was performed on 150 cancer patients (71 females and 79 males) admitted to the hospitals affiliated with Kermanshah University of Medical Sciences. Endler and Parker Coping Inventory for Stressful Situations, and World Health Organization's Quality of Life Questionnaire were used to evaluate their coping style and QOL, respectively. RESULTS: The Present study showed in cancer patients being male, single, having higher salary and education, and lower age are related to higher QOL. Furthermore, in general, QOL of cancer patients was positively correlated with avoidant coping style (P < 0.05, r : 0.170) and negatively associated with emotion-focused coping styles (P < 0.01, r : -0.378). CONCLUSION: The results suggested that focusing on a patient's coping style, predominantly on an emotion-focused coping style, is essential to improve patient's QOL, and that patients possibly to employ a more emotion-oriented coping style should receive enough notice, particularly before discharge.

Severe refeeding syndrome after starvation ketoacidosis requiring stopping feeds.

INTRODUCTION: Starvation ketoacidosis (SKA) is a rare cause of ketoacidosis in the general population but can be seen with malignancy. Patients often respond well to treatment, but some rarely develop refeeding syndrome (RFS) as their electrolytes drop to dangerous levels causing organ failure. Typically, RFS can be managed with low-calorie feeds, but sometimes patients require a halt in feeds until their electrolyte imbalances are managed. CASE REPORT: We discuss a woman with synovial sarcoma on chemotherapy who was diagnosed with SKA and then developed severe RFS after treatment with intravenous dextrose. Phosphorus, potassium, and magnesium levels dropped precipitously and remained fluctuant for 6 days. She also developed normal sinus ventricular tachycardia, premature ventricular beats, and bigeminy. She could not tolerate calorie supplementation at that time. She was managed with electrolyte repletions until clinically stable and then progressed to a liquid diet. DISCUSSION: We present a unique case of severe SKA that resulted in RFS requiring nihil per orem (NPO) treatment for 6 days. There are no specific guidelines for SKA or RFS management. Patients with pH < 7.3 may benefit from baseline serum phosphorus, potassium, and magnesium levels. Clinical trials are needed to further study which patients may benefit from starting at a low-calorie intake versus those that require holding nutrition until clinically stable. CONCLUSION: Completely stopping caloric intake until a patient's electrolyte imbalance improves is an important management aspect of RFS to underscore and study, as grave complications can occur even with cautious refeeding regimens.

Advances in Autosomal Dominant Polycystic Kidney Disease: A Clinical Review.

Polycystic kidney disease (PKD) is a multiorgan disorder resulting in fluid-filled cyst formation in the kidneys and other systems. The replacement of kidney parenchyma with an ever-increasing volume of cysts eventually leads to kidney failure. Recently, increased understanding of the pathophysiology of PKD and genetic advances have led to new approaches of treatment targeting physiologic pathways, which has been proven to slow the progression of certain types of the disease. We review the pathophysiologic patterns and recent advances in the clinical pharmacotherapy of autosomal dominant PKD. A multipronged approach with pharmacologic and nonpharmacologic treatments can be successfully used to slow down the rate of progression of autosomal dominant PKD to kidney failure.

A case of renal and splenic LECT 2 amyloidosis: A recently recognized cause of renal and systemic amyloidosis.

Amyloidosis has traditionally been of a few defined varieties, most commonly including light-chain amyloidosis (AL amyloidosis) and secondary amyloidosis due to chronic inflammation (AA amyloidosis). Apolipoprotein A-I/A-II cystatin C, gelsolin, lysozyme, fibrinogen alpha chain, beta 2 microglobulin, and transthyretin familial amyloidosis represent rarer but reported varieties. Ten years ago, the first reports linked leukocyte chemotactic factor 2 (LECT2) amyloidosis as a pathological agent identified as a novel class of amyloid-generating protein. Epidemiology suggested that this was a new cause of amyloidosis that is especially common in Hispanic patients and somewhat common among patients from the Middle East-North Africa (MENA) region. We report a case of splenic and renal LECT 2 amyloidosis in a 62-year- old Hispanic male with diabetes mellitus. After an unremarkable serological workup, LECT 2 amyloidosis was diagnosed on renal biopsy. The case presentation is reviewed as a typical presentation, and the literature is reviewed regarding this newly reported entity, resulting in infiltrative renal amyloidosis and chronic renal disease.

Diverse Clinical Presentations of C3 Dominant Glomerulonephritis.

C3 dominant immunofluorescence staining is present in a subset of patients with idiopathic immune complex membranoproliferative glomerulonephritis (iMPGN). It is increasingly recognized that iMPGN may be complement driven, as are cases of "typical" C3 glomerulopathy (C3G). In both iMPGN and C3G, a frequent membranoproliferative pattern of glomerular injury may indicate common pathogenic mechanisms via complement activation and endothelial cell damage. Dysregulation of the alternative complement pathway and mutations in certain regulatory factors are highly implicated in C3 glomerulopathy (which encompasses C3 glomerulonephritis, dense deposit disease, and cases of C3 dominant MPGN). We report three cases that demonstrate that an initial biopsy diagnosis of iMPGN does not exclude complement alterations similar to the ones observed in patients with a diagnosis of C3G. The first patient is a 39-year-old woman with iMPGN and C3 dominant staining, with persistently low C3 levels throughout her course. The second case is a 22-year-old woman with elevated anti-factor H antibodies and C3 dominant iMPGN findings on biopsy. The third case is a 25-year-old woman with C3 dominant iMPGN, dense deposit disease, and a crescentic glomerulonephritis on biopsy. We present the varied phenotypic variations of C3 dominant MPGN and review clinical course, complement profiles, genetic testing, treatment course, and peri-transplantation plans. Testing for complement involvement in iMPGN is important given emerging treatment options and transplant planning.

Equivalent Efficacy and Decreased Rate of Overcorrection in Patients With Syndrome of Inappropriate Secretion of Antidiuretic Hormone Given Very Low-Dose Tolvaptan.

RATIONALE & OBJECTIVE: Euvolemic hyponatremia often occurs due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Vasopressin 2 receptor antagonists may be used to treat SIADH. Several of the major trials used 15 mg of tolvaptan as the lowest effective dose in euvolemic and hypervolemic hyponatremia. However, a recent observational study suggested an elevated risk for serum sodium level overcorrection with 15 mg of tolvaptan in patients with SIADH. STUDY DESIGN: A retrospective chart review study comparing outcomes in patients with SIADH treated with 15 versus 7.5 mg of tolvaptan. SETTINGS & PARTICIPANTS: Patients with SIADH who were treated with a very low dose of tolvaptan (7.5 mg) at a single center compared with patients using a 15-mg dose from patient-level data from the observational study described previously. PREDICTORS: Tolvaptan dose of 7.5 versus 15 mg daily. OUTCOMES: Appropriate response to tolvaptan, defined as an initial increase in serum sodium level > 3 mEq/L, and overcorrection of serum sodium level (>8 mEq/L per day, and >10 mEq/L per day in sensitivity analyses). ANALYTICAL APPROACH: Descriptive study with additional outcomes compared using t tests and F-tests (Fischer's Exact χ2 Test). RESULTS: Among 18 patients receiving 7.5 mg of tolvaptan, the mean rate of correction was 5.6 ± 3.1 mEq/L per day and 2 (11.1%) patients corrected their serum sodium levels by >8 mEq/L per day, with 1 of these increasing by >12 mEq/L per day. Of those receiving tolvaptan 7.5 mg, 14 had efficacy, with increases ≥ 3 mEq/L; similar results were seen with the 15-mg dose (21 of 28). There was a statistically significant higher chance of overcorrection with the use of 15 versus 7.5 mg of tolvaptan (11 of 28 vs 2 of 18; P = 0.05; and 10 of 28 vs 1 of 18; P = 0.03, for >8 mEq/L per day and >10 mEq/L per day, respectively). LIMITATIONS: Small sample size, retrospective, and nonrandomized. CONCLUSIONS: Tolvaptan, 7.5 mg, daily corrects hyponatremia with similar efficacy and less risk for overcorrection in patients with SIADH versus 15 mg of tolvaptan.

Blood Pressure and Living Kidney Donors: A Clinical Perspective.

Elevated blood pressure (BP), or "hypertension," has been one of the main exclusion criteria for living kidney donation, as it is a risk factor for renal and cardiovascular disease. The effect of elevated BP in living kidney donors is not well studied or understood. The most current living kidney donation guidelines state that donors with a BP >140/90 mm Hg with 1-2 antihypertensive medications or evidence of end-organ damage should be excluded from living kidney donation. Yet, the definitions of "hypertension" have changed with the release of the American Heart Association (AHA)/American College of Cardiology (ACC) clinical practice guidelines suggesting that 120-129 mm Hg is elevated BP and Stage 1 hypertension is 130 mm Hg. However, the kidney function (in terms of estimated GFR) of "hypertensive" living kidney donors does not fare significantly worse postdonation compared with that of "normotensive" donors. In addition, even though living kidney donation itself is not considered to be a risk factor for developing hypertension, there exist certain risk factors (African American or Hispanic descent, obesity, age) that may increase the risk of living kidney donors developing elevated BP postdonation. The choice of BP targets and medications needs to be carefully individualized. In general, a BP <130/80 mm Hg is needed, along with lifestyle modifications.

Secondary membranous nephropathy in a patient with myasthenia gravis without thymic disease, and partial remission induced by adrenocorticotropic hormone therapy.

Membranous glomerulonephritis is the most common glomerular disease in adults. Its primary form has been characterized with formation of phospholipase A2 receptor antibodies. Malignancy, infections, and autoimmune disorders are the most common causes of secondary membranous glomerulonephritis. We present a case of a 55-year-old African American female who presented with nephrotic range proteinuria and diagnosed with secondary membranous glomerulonephritis based on distinct pathological features on kidney biopsy and absence of serum phospholipase A2 receptor antibodies. She initially underwent extensive workup for malignancies, infections, and common autoimmune disorders which were all negative. Her proteinuria remained resistant to steroid treatment and she was treated with subcutaneous adrenocorticotropic hormone injections. Meanwhile, she was also diagnosed with the anti-muscle specific kinase antibody variant of myasthenia gravis. In literature, there are few case reports of myasthenia gravis as a cause of secondary membranous glomerulonephritis. In our case, the lack of other inciting factors also suggested this association.

Everolimus worsening chronic proteinuria in patient with diabetic nephropathy post liver transplantation.

Mammalian target of rapamycin (mTOR) inhibitors are used in renal sparing protocols and transplant immunosuppression in patients with solid organ and stem cell transplants. They cause various side effects, including proteinuria, which is mediated by blockade of the vascular endothelial growth factor receptor pathway. There have been various reports of mTOR inhibitors causing proteinuria or worsening proteinuria form preexisting renal glomerulo-pathies. We report a 73-year old male with diabetic glomerulosclerosis, acute liver failure due to Budd-Chiari syndrome, chronic low platelets, and worsening proteinuria from 0.46 g protein/g creatinine to 2.2 g protein/g creatinine. Workup revealed no thrombotic microangiopathy through skin biopsy, and a renal biopsy confirmed only clinically suspected diabetic and hypertensive glomerulosclerosis and possible calcineurin inhibitors. On discontinuation of everolimus urine protein decreased back to 0.6 g/g creatinine. We review the mechanism of mTOR-induced proteinuria and how this may affect diabetic nephropathy secondarily. We also consider the clinical implications of this in transplant patients receiving these agents.

Primary membranous nephropathy with concomitant IgA nephropathy.

Membranous nephropathy (MN), an autoimmune glomerulonephritis which can occur in primary and secondary forms, is one of the most common inflammatory glomerulopathies in elderly patients. The pathophysiology of the primary form is generally due to circulating immunoglobulin (IgG4) antibodies which often target phospholipase A2 receptors (anti-PLA2R) and Thrombospondin Type 1 Domain containing 7A (anti THSD7A). IgA nephropathy is one of the most common autoimmune glomerular diseases in the world and presents with a spectrum of disease ranging from asymptomatic mild hematuria and proteinuria to rapidly progressive crescentic glomerulonephritis. We present a rare case of concomitant IgA and primary MN in a single patient treated successfully with renin-angiotensin-aldosterone blockade, corticosteroids, and calcineurin inhibitors. The peak proteinuria was near 7.5-8 g protein/g creatinine by various measures. Serum creatinine remained normal, and anti-PLA2R was detectable and decreased with successful treatment. Clinicians should be aware of the possibility of two glomerular disorders in patients with glomerulonephritis and atypical presentations for any single disorder.

Three Patients with Lithium-Associated Hyperparathyroidism: Literature Review Regarding Medical and Surgical Management.

Lithium (Li) carbonate has been established as a mood stabilizer and an efficacious treatment for bipolar disorder since its discovery by Dr. John Cade in 1948. Li interacts significantly with organ systems and endocrine pathways. One of the most challenging side effects of Li to manage is its effect on the parathyroid glands. Dysregulation of parathyroid signaling due to Li results in hypercalcemia due to increased vitamin D3 generation, increased calcium absorption from the gut, and bone resorption, occasionally resulting in concomitant hypercalciuria. However, hypercalciuria is not a definitive feature for hyperparathyroidism, and normal calcium excretion might be seen in these patients. Hypercalcemia may also result from volume contraction and decreased renal clearance, which are commonly seen in these patients. Anatomically the parathyroid abnormalities can present as single or multiglandular disease. We report 3 cases where the patients developed multiple side effects of Li therapy as well as hypercalcemia due to hyperparathyroidism. The literature is reviewed with regard to medical and surgical management of Li-associated hyperparathyroidism in the context of these 3 presented cases.

Hypercalcemia-induced acute kidney injury in a Caucasian female due to radiographically silent systemic sarcoidosis.

. Sarcoidosis is a rare autoimmune disease resulting in formation of non-necrotizing "non-caseating" granulomas generally in the lung. The disease classically strikes African American females in their fourth and fifth decades. The resulting hypercalcemia is a result of 1-α hydroxylase overexpression in granulomas with increased 1,25-dihydroxy vitamin D levels. This phenomenon can also be observed in mycobacterial and fungal infections that produce granulomas in infected patients. Thus, chronic infectious diseases are part of differential diagnosis of granulomatous processes. We present an elderly Caucasian female who presented with hypercalcemia with serum calcium of 11 - 14 mg/dL and an elevated ionized calcium of 1.4 - 1.5 mmol/L. Initially cholecalciferol supplements were stopped, but hypercalcemia persisted for more than 2 months. 1,25-dihydroxy vitamin D levels were markedly elevated with low normal 25-hydroxy vitamin D levels, angiotensin-converting enzyme levels were also high, and chest computed tomography (CT) imaging was negative for any lymphadenopathy (including perihilar lymphadenopathy). Malignancy and infectious workups were negative for fungal and mycobacterial infections. Positron emission tomography revealed several small lymph nodes in right upper lobe of lung, and biopsy of bone marrow and lung lymph-nodes revealed non-caseating granulomata. We present an atypical case of occult sarcoidosis presenting mainly with biochemical findings without any definitive imaging findings, making diagnosis a clinical challenge.

Antineutrophil cytoplasmic antibody-associated vasculitis, update on molecular pathogenesis, diagnosis, and treatment.

Circulating antineutrophil cytoplasmic antibodies (ANCAs) are the central pathogenic mechanism for a group of systemic and renal syndromes called the ANCA-associated vasculitis (AAV). The nomenclature has changed from eponymous labeling to granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. These syndromes predominantly affect the pulmonary and renal systems. We also review the molecular pathology behind ANCAs and associated antigens and infections. Various clinical presentations, the multiple target organs affected, and diagnostic challenges involved in identifying these diseases are discussed. Treatment updates are also provided with regard to new studies and the now standard use of anti-CD-20 monoclonal antibodies as first-line therapy in all but the most aggressive presentations of this disease. Maintenance regimens and monitoring strategies for relapse of vasculitis and associated systemic complications are discussed.

Case Report: Patient with Hepatitis C, p-ANCA, and Cryoglobulin Antibodies Presenting with Necrotizing Crescentic p-ANCA Glomerulonephritis.

Hepatitis C (HCV) infection has a prevalence of 3 million infected individuals in the United States, according to recent Center for Disease Control reports, and can have various renal manifestations. Cryoglobulins, antibodies that precipitate at colder temperatures in vitro, are a relatively common cause of renal disease in HCV infection. The cryoglobulin proteins can form occlusive aggregates in small glomerular capillary lumina or deposit in other areas of the glomerulus, resulting in hypocomplementemia, proteinuria, hematuria, and renal injury. The typical biopsy pattern is that of membranoproliferative glomerulonephritis (MPGN). There are, however, other HCV-related patterns of glomerular injury. Anti-neutrophil cytoplasmic antibodies (ANCA) are known to exist in HCV-infected patients. In many reported cases, ANCA serologic testing may appear positive due to cross-reactivity of the immune assays; however, the biopsy findings do not support ANCA-associated crescentic glomerulonephritis (GN)/vasculitis as the primary cause of glomerular injury. There are rare reports of microscopic polyangiitis (MPA) p-ANCA vasculitis, in patients with HCV infection. In comparison with the MPGN pattern of cryoglobulinemic glomerular injury, biopsies from these HCV-infected patients with concomitant MPA revealed a crescentic GN, associated with normal serum complement levels. We present a case of HCV-associated glomerular disease with the surprising biopsy finding of necrotizing and crescentic p-ANCA GN, with a background, low-grade mesangial immune complex GN. Thus, p-ANCA disease should also be considered in HCV-infected patients, in addition to the more typical lesions of MPGN or cryoglobulinemic GN.

Acute Kidney Injury after Pembrolizumab-Induced Adrenalitis and Adrenal Insufficiency.

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein 1 (PD-1) antigen and induces an immune response against tumor tissues. It has been successful in inducing remission in patients with severe metastatic disease, often refractory to other chemotherapeutic agents. The risk of injury of other organ systems has been noted with reported cases of glomerular disease and endocrine disease. In addition, hypophysitis as well as dermatological and gastroenterological side effects have been reported. Renal injury with immune checkpoint inhibitors like nivolumab and pembrolizumab is usually mediated via interstitial nephritis, though glomerular disease presentations like anti-neutrophil cytoplasmic antibody-associated vasculitis, immune complex disease, and thrombotic microangiopathy have also been reported. We report a 70-year-old Caucasian male who underwent treatment with pembrolizumab for adenocarcinoma of the lung. He developed acute adrenal insufficiency and concomitant severe hypotension upon presentation. He did not require renal replacement therapy, rather his severe acute kidney injury resolved with hydration, normalization of blood pressures with vasopressors, and treatment with high-dose corticosteroids. His urinary indices (fractional excretion of urea, FEUrea) and clinical course were highly suspicious for acute tubular necrosis that resolved quickly after treating his underlying adrenalitis. The urinary sediment, proteinuria, and clinical course were not typical for the usually expected renal lesion of interstitial nephritis in patients treated with immune checkpoint inhibitors.

Eccrine Nevus Presenting with Umbilical Discharge: A Case Report and Review of the Literature.

Eccrine nevus is a rare skin lesion with protean manifestations like hyperhidrosis, discolored nodules, papules, and so forth, which has been reported in various anatomic parts of the body including the forearm, leg, thigh, back, and coccyx. Our patient was a 26-year-old male, who presented with increasing colorless and odorless episodic umbilical discharge. First impression for the patient was an umbilical sinus and the patient underwent surgery. Histopathological study revealed the lesion to be an eccrine nevus of the umbilicus. This is the first case of eccrine nevus presenting with umbilical discharge. We recommend that eccrine nevus should be considered as a differential diagnosis for umbilical discharge.