Mental Health and Autosomal Dominant Polycystic Kidney Disease: A Narrative Review.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder marked by the development of cysts in the kidneys and other organs, leading to diverse clinical manifestations, including kidney failure. The psychological burden of ADPKD is substantial, with significant contributors including pain, daily life disruptions, depression, anxiety, and the guilt associated with transmitting ADPKD to offspring. This review details the psychological impacts of ADPKD on patients, addressing how they navigate physical and emotional challenges, including pain management, genetic guilt, mood disorders, and disease acceptance. This review also underscores the need for comprehensive research into the psychological aspects of ADPKD, focusing on the prevalence and contributing factors of emotional distress, and identifying effective strategies for managing anxiety and depression. Furthermore, it highlights the importance of understanding the diverse factors that influence patients' quality of life and advocates for holistic interventions to address these psychological challenges.

Risk factors for in-hospital mortality among patients hospitalized with COVID-19 and end-stage kidney disease.

AIMS: The mortality rate for -COVID-19 infection varies significantly depending on age and comorbidities but remains high in hospitalized patients overall. Several retrospective studies have identified patients with end-stage kidney disease (ESKD) to be at increased risk. The objective of this study was to study in-hospital outcomes of ESKD patients at an academic medical center and identify characteristics that place them at a higher risk for in-hospital mortality. MATERIALS AND METHODS: A retrospective chart review was conducted including adult patients (≥ 18 years old) admitted to Loma Linda Medical Center for COVID-19 infection with a previous diagnosis of ESKD. Patients with prior kidney transplants were excluded. The main outcome of this study was the rate of in-hospital mortality. RESULTS: 21 of the 91 patients died with a mortality rate of 23%. Age, D-dimer > 0.4 µg/mL, ejection fraction less than 50%, and ferritin > 300 ng/mL were predictors for mortality in unadjusted univariate analysis. Adjusted multivariable analysis demonstrated that only an ejection fraction of less than 50% was associated with increased mortality risk. CONCLUSION: Cardiovascular disease is the leading cause of mortality for ESKD patients and also places them at increased risk of mortality in the setting of severe COVID-19 infection.

Lupus nephritis: management challenges during pregnancy.

Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), leads to significant kidney inflammation and damage and drastically increases mortality risk. Predominantly impacting women in their reproductive years, LN poses specific risks during pregnancy, including pre-eclampsia, growth restrictions, stillbirth, and preterm delivery, exacerbated by lupus activity, specific antibodies, and pre-existing conditions like hypertension. Effective management of LN during pregnancy is crucial and involves carefully balancing disease control with the safety of the fetus. This includes pre-conception counseling and a multidisciplinary approach among specialists to navigate the complexities LN patients face during pregnancy, such as distinguishing LN flare-ups from pregnancy-induced conditions. This review focuses on exploring the complex dynamics between pregnancy and LN, emphasizing the management difficulties and the heightened risks pregnant women with LN encounter.

Delayed-Release Budesonide in a Patient With Progressive IgA Nephropathy and Stage 4 Chronic Kidney Disease: A Case Report.

Delayed-release (DR) budesonide received expedited approval from the US Food and Drug Administration (FDA) as a treatment for reducing proteinuria in individuals with primary IgA nephropathy (IgAN) who are at significant risk of disease progression. The approval was based on clinical trials primarily involving patients with an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m2. However, the efficacy of DR budesonide in reducing kidney function decline, especially in patients with an eGFR less than 30 mL/min/1.73 m2 and proteinuria less than 1 g/d, remains unclear. We report the case of a 43-year-old man with a long-term history of hypertension and biopsy-proven IgAN who experienced a progressive increase in proteinuria and serum creatinine, along with a decline in eGFR to 28 mL/min/1.73 m2 despite maximal supportive management. Following therapy with DR budesonide, a decreasing trend in proteinuria and a stabilization of eGFR were observed in the recent measurements. While initial data suggested the effectiveness of DR budesonide primarily in patients with an eGFR over 30 mL/min/1.73 m2, our case demonstrates the potential of DR budesonide for use in scenarios beyond its currently approved indications. This underscores the need for additional research on patients with advanced stages of chronic kidney disease.

Marginal Zone Lymphoma Manifesting as Macrophage Activation Syndrome: A Case Report.

Macrophage activation syndrome (MAS) is a form of secondary hemophagocytic lymphohistiocytosis (HLH) when it occurs in the context of rheumatologic disorders. HLH is a rare and potentially life-threatening syndrome characterized by excessive immune system activation. It is mainly seen in children and can be genetic based or related to infections, malignancies, rheumatologic disorders, or immunodeficiency syndromes. MAS can present with nonspecific symptoms, leading to a delay in diagnosis. This report describes a case of a 64-year-old female with marginal zone lymphoma and systemic lupus erythematosus who presented with a purpuric rash and acute kidney injury. She underwent a kidney biopsy and was diagnosed with MAS. This case highlights the importance of promptly recognizing MAS's symptoms and signs, allowing timely diagnosis and early therapeutic intervention. This potentially fatal condition tends to respond well to rapid treatment initiation with corticosteroids and to address the underlying condition.

AIDS-Associated BK Virus Nephropathy in Native Kidneys: A Case Report and Review of the Literature.

BK virus (BKV) is a small DNA virus, a member of the polyomavirus family, that causes an opportunistic infection in immunocompromised patients, especially kidney transplant patients. This virus establishes a lifelong infection in most of the population, and once it reactivates in an immunocompromised state, leads to BKV nephropathy. This review seeks to assess the correlation between severe immunosuppression, evident by low CD4 cell counts in HIV-positive patients, and the reactivation of BKV, causing nephropathy. A literature review was conducted, extracting, and analyzing case reports of HIV-positive patients showing correlations between their degree of immunosuppression, as evidenced by their CD4 counts, and the degree of BKV infectivity, confirmed by kidney biopsy. A total of 12 cases of BKV nephropathy in HIV-infected patients were reviewed. A common finding was the presence of profound immunosuppression, with most patients having CD4 counts ≤50 cells/ mm3. A substantial number also had comorbid malignancies, with some undergoing chemotherapy, potentially increasing the risk of BKV reactivation. In addition to the HIV status and malignancies, other risk factors for BKV reactivation included older age, male gender, diabetes mellitus, Caucasian race, and ureteral stent placement. BKV nephropathy in HIV patients with native kidneys is closely correlated with severe immunosuppression. Although therapeutic strategies exist for post-transplant patients, aside from the treatment of HIV with highly active anti-retroviral therapy (HAART), which potentially helps with clearing BKV by increasing CD4 count, there is no definitive treatment for a native kidney BKV nephropathy in patients with AIDS. The complexity of the cases and severity of comorbidities indicate the need for further research to develop therapeutic strategies tailored to this population.

Diuretic Use in Post-Kidney Transplant Patients: A Retrospective Chart Review.

BACKGROUND: The occurrence of delayed graft function (DGF) significantly enhances the possibility of both acute and chronic rejection of the transplanted organ, thereby reducing patient quality of life and survival rates. To prevent and manage oliguria in renal transplant patients, loop diuretics are presently commonly used. In our study, we assessed the possible impact of furosemide on the incidence of DGF among kidney transplant recipients. METHODS: A review of medical records was conducted to examine demographic characteristics and kidney transplant outcomes in an adult (older than 18 years old) population. The primary objective was to determine the incidence of delayed graft function (DGF), whereas the secondary objective was to compare the creatinine levels and estimated glomerular filtration rate (eGFR) at day 30 and day 90 post-transplantation in patients who were administered furosemide vs those who were not. RESULTS: This study included 330 patients who underwent kidney transplantation. Furosemide was administered to 169 (51.3%), whereas 161(48.7%) patients did not receive continued dose of diuretic postoperatively. The rate of DGF was significantly higher in patients who received furosemide than in those who did not (furosemide 44% vs 4%; P < .001). The eGFR was lower in the furosemide group compared to the no furosemide group at day 30 (56 ± 24 vs 71 ± 24 mL/min/1.73 m2, P < .001) and day 90 (66 ± 27 vs 78 ± 25 mL/min/1.73 m2, P < .001). CONCLUSIONS: Our results show that there is no benefit in treating an oliguric AKI with furosemide. Administration of furosemide, especially in high doses, may increase the risk of toxicity, delay dialysis, and increase the length of stay.

Calciphylaxis in a Patient With Lupus Nephritis and Acute Kidney Injury: A Rare Case Report and Literature Review.

Calciphylaxis is a rare and severe disease characterized by calcification, fibrosis, and thrombosis of small blood vessels. Although it primarily affects patients with end-stage renal disease (ESRD) on dialysis, limited cases have been reported of calciphylaxis in patients with acute kidney injury (AKI) and lupus. This case report describes the occurrence of calciphylaxis in a 35-year-old female recently diagnosed with lupus nephritis class IV and AKI requiring dialysis.

IgA nephropathy: a review of existing and emerging therapies.

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. Recently, there have been multiple advances in the understanding of IgAN pathophysiology and therapeutic options. Despite the advent of new treatment options, individual risk stratification of the disease course and choosing the best treatment strategy for the patient remains challenging. A multitude of clinical trials is ongoing, opening multiple opportunities for enrollment. In this brief review we discuss the current approach to the management of IgAN and highlight the ongoing clinical trials.

Early Resumption of Peritoneal Dialysis Post Laparoscopic Appendectomy: A Case Report and Literature Review.

Abdominal pain and fever in patients on peritoneal dialysis (PD) raise suspicion of PD-associated peritonitis. However, other causes of peritonitis such as appendicitis should be considered. The laparoscopic approach is the standard of care in many of these situations. This technique allows PD catheter preservation and early resumption of PD. Here, we report a case where PD was resumed successfully 48 hours after laparoscopic appendectomy. A 45-year-old man with end-stage renal disease on chronic PD presented with acute abdominal pain. On examination, the patient was febrile and had lower abdomen tenderness without a rebound. The exit site of the PD catheter was clean. An initial diagnosis of PD-associated peritonitis was made, and an intraperitoneal antibiotic was given. Abdominal computed tomography revealed appendicitis. It was confirmed that the patient had severe nonperforated appendicitis following a laparoscopic appendectomy. The PD catheter was preserved, although the patient reported good residual kidney function; his electrolyte abnormalities with rising creatinine and potassium indicated the need to resume dialysis. Low-volume PD in a strict supine position was resumed 48 hours after surgery. The patient tolerated low-fill PD without any complications. He was discharged home on post-op day 4, and further follow-up revealed no complications. Resuming PD early in patients who go under laparoscopic surgery with low-volume PD is a reasonable option in select cases. Close follow-up from the dialysis team to detect and manage complications is necessary.

Combination therapy of insulin-like growth factor I and BTP-2 markedly improves lipopolysaccharide-induced liver injury in mice.

Acute liver injury is a common disease without effective therapy in humans. We sought to evaluate a combination therapy of insulin-like growth factor 1 (IGF-I) and BTP-2 in a mouse liver injury model induced by lipopolysaccharide (LPS). We chose this model because LPS is known to increase the expression of the transcription factors related to systemic inflammation (i.e., NFκB, CREB, AP1, IRF 3, and NFAT), which depends on calcium signaling. Notably, these transcription factors all have pleiotropic effects and account for the other observed changes in tissue damage parameters. Additionally, LPS is also known to increase the genes associated with a tissue injury (e.g., NGAL, SOD, caspase 3, and type 1 collagen) and systemic expression of pro-inflammatory cytokines. Finally, LPS compromises vascular integrity. Accordingly, IGF-I was selected because its serum levels were shown to decrease during systemic inflammation. BTP-2 was chosen because it was known to decrease cytosolic calcium, which is increased by LPS. This current study showed that IGF-I, BTP-2, or a combination therapy significantly altered and normalized all of the aforementioned LPS-induced gene changes. Additionally, our therapies reduced the vascular leakage caused by LPS, as evidenced by the Evans blue dye technique. Furthermore, histopathologic studies showed that IGF-I decreased the proportion of hepatocytes with ballooning degeneration. Finally, IGF-I also increased the expression of the hepatic growth factor (HGF) and the receptor for the epidermal growth factor (EGFR), markers of liver regeneration. Collectively, our data suggest that a combination of IGF-I and BTP-2 is a promising therapy for acute liver injury.

Calcium released by osteoclastic resorption stimulates autocrine/paracrine activities in local osteogenic cells to promote coupled bone formation.

A major cause of osteoporosis is impaired coupled bone formation. Mechanistically, both osteoclast-derived and bone-derived growth factors have been previously implicated. Here, we hypothesize that the release of bone calcium during osteoclastic bone resorption is essential for coupled bone formation. Osteoclastic resorption increases interstitial fluid calcium locally from the normal 1.8 mM up to 5 mM. MC3T3-E1 osteoprogenitor cells, cultured in a 3.6 mM calcium medium, demonstrated that calcium signaling stimulated osteogenic cell proliferation, differentiation, and migration. Calcium channel knockdown studies implicated calcium channels, Cav1.2, store-operated calcium entry (SOCE), and calcium-sensing receptor (CaSR) in regulating bone cell anabolic activities. MC3T3-E1 cells cultured in a 3.6 mM calcium medium expressed increased gene expression of Wnt signaling and growth factors platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and bone morphogenic protein-2 (BMP 2). Our coupling model of bone formation, the receptor activator of nuclear factor-κΒ ligand (RANKL)-treated mouse calvaria, confirmed the role of calcium signaling in coupled bone formation by exhibiting increased gene expression for osterix and osteocalcin. Critically, dual immunocytochemistry showed that RANKL treatment increased osterix-positive cells and increased fluorescence intensity of Cav1.2 and CaSR protein expression per osterix-positive cell. The above data established that calcium released by osteoclasts contributed to the regulation of coupled bone formation. CRISPR/Cas-9 knockout of Cav1.2 in osteoprogenitor cells cultured in basal calcium medium caused a >80% decrease in the expression of downstream osteogenic genes, emphasizing the large magnitude of the effect of calcium signaling. Thus, calcium signaling is a major regulator of coupled bone formation.

Vascular access in therapeutic apheresis: One size does not fit all.

BACKGROUND: Therapeutic apheresis has been used in treating hematological and non-hematological diseases. For a successful procedure, efficient vascular access is required. Presently, peripheral venous access (PVA), central venous catheterization (CVC), implantable ports, and arteriovenous fistulas (AVFs) are used. This review aims to evaluate different type of access and their pros and cons to help physicians determine the best venous access. METHODS: The electronic search included PubMed and Google Scholar up to November 2020. The Mesh terms were apheresis, peripheral catheterization, central catheterization, and arteriovenous fistula. RESULTS: A total of 228 studies were found through database searching. Two independent authors reviewed the articles using their titles and abstracts; 88 articles were selected and the full text was reviewed. Finally, 26 were included. The inclusion criteria were studies incorporating patients with any indication for apheresis. CONCLUSION: PVA has been promoted in recent years in many centers across the United States to lower the rate of complications associated with vascular access and to make this procedure more accessible. Several factors are involved in selecting appropriate venous access, such as the procedure's duration and frequency, patient's vascular anatomy, and staff's experience. In short-term procedures, temporary vascular access like PVA or CVC is preferred. Permanent vascular access such as AVF, tunneled cuffed central lines, and implantable ports are more beneficial in prolonged treatment period but each patient has to be evaluated individually by apheresis team for the most appropriate method.

Mortality Benefit From the Passive Leg Raise Maneuver in Guiding Resuscitation of Septic Shock Patients: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Fluid therapy plays a major role in the management of critically ill patients. Yet assessment of intravascular volume in these patients is challenging. Different invasive and non-invasive methods have been used with variable results. The passive leg raise (PLR) maneuver has been recommended by international guidelines as a means to determine appropriate fluid resuscitation. We performed this systematic review and meta-analysis to determine if using this method of volume assessment has an impact on mortality outcome in patients with septic shock. METHODS: This study is a systematic review and meta-analysis. We searched available data in the MEDLINE, CINAHL, EMBASE, and CENTRAL databases from inception until October 2020 for prospective, randomized, controlled trials that compared PLR-guided fluid resuscitation to standard care in adult patients with septic shock. Our primary outcome was mortality at the longest duration of follow-up. RESULTS: We screened 1,425 article titles and abstracts. Of the 23 full-text articles reviewed, 5 studies with 462 patients met our eligibility criteria. Odds ratios (ORs) and associated 95% confidence intervals (CIs) for mortality at the longest reported time interval were calculated for each study. Using random effects modeling, the pooled OR (95% CI) for mortality with a PLR-guided resuscitation strategy was 0.82 (0.52 -1.30). The included studies were not blinded and they ranged from having low to high risk of bias using the Cochrane Risk of Bias Tool. CONCLUSION: Our analysis showed there was no statistically significant difference in mortality among septic shock patients treated with PLR-guided resuscitation vs. those with standard care.

Comparison of Outcomes in Patients Undergoing Renal Transplantation With Impaired vs Normal Left Ventricular Ejection Fraction.

BACKGROUND: Renal transplantation improves long-term outcomes in patients with end-stage renal disease (ESRD); however, patients with impaired left ventricular ejection fraction (LVEF) are less likely to be selected for renal transplantation. We sought to evaluate the effect of renal transplantation in this population. METHODS: We retrospectively evaluated 181 patients who underwent renal transplantation between 2011 and 2016. For patients with pretransplant LVEF <50% (cohort 1) and ≥50% (cohort 2), we evaluated the effect of renal transplantation on LVEF, graft failure, and mortality. RESULTS: Cohort 1 comprised 24 patients (mean age, 47 years; pretransplant LVEF 38%). Cohort 2 comprised 157 patients (mean age, 53 years; pretransplant LVEF 64%). Forty-six percent of cohort 1 experienced significant improvement in LVEF posttransplant, with mean LVEF improvement from 38% to 66%. There was no significant association between pretransplant LVEF and graft failure (hazard ratio [HR] = 2.7; 95% confidence interval [CI], 0.6-11.4; P = .1) or mortality (HR = 1.02; 95% CI, 0.3-3.6; P = .9). Coronary artery disease predicted mortality (HR = 3.12; 95% CI, 1.2-8.4; P = .02). Older age trended toward higher mortality (HR = 1.04; 95% CI, 1.0-1.1; P = .05). Younger age predicted graft failure (HR = 0.96; 95% CI, 0.8-0.9; P = .02). CONCLUSIONS: In patients with ESRD undergoing renal transplantation, there was no significant association between pretransplant LVEF and mortality or graft failure, suggesting that patients with ESRD with impaired LVEF can experience positive posttransplant outcomes.

The Effects of Insulin-Like Growth Factor I and BTP-2 on Acute Lung Injury.

Acute lung injury (ALI) afflicts approximately 200,000 patients annually and has a 40% mortality rate. The COVID-19 pandemic has massively increased the rate of ALI incidence. The pathogenesis of ALI involves tissue damage from invading microbes and, in severe cases, the overexpression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). This study aimed to develop a therapy to normalize the excess production of inflammatory cytokines and promote tissue repair in the lipopolysaccharide (LPS)-induced ALI. Based on our previous studies, we tested the insulin-like growth factor I (IGF-I) and BTP-2 therapies. IGF-I was selected, because we and others have shown that elevated inflammatory cytokines suppress the expression of growth hormone receptors in the liver, leading to a decrease in the circulating IGF-I. IGF-I is a growth factor that increases vascular protection, enhances tissue repair, and decreases pro-inflammatory cytokines. It is also required to produce anti-inflammatory 1,25-dihydroxyvitamin D. BTP-2, an inhibitor of cytosolic calcium, was used to suppress the LPS-induced increase in cytosolic calcium, which otherwise leads to an increase in proinflammatory cytokines. We showed that LPS increased the expression of the primary inflammatory mediators such as toll like receptor-4 (TLR-4), IL-1ß, interleukin-17 (IL-17), TNF-α, and interferon-γ (IFN-γ), which were normalized by the IGF-I + BTP-2 dual therapy in the lungs, along with improved vascular gene expression markers. The histologic lung injury score was markedly elevated by LPS and reduced to normal by the combination therapy. In conclusion, the LPS-induced increases in inflammatory cytokines, vascular injuries, and lung injuries were all improved by IGF-I + BTP-2 combination therapy.

Use of angiotensin converting enzyme inhibitors in patients receiving therapeutic plasma exchange with a centrifuge-based apheresis system.

Angiotensin-converting enzyme inhibitors (ACEi) are frequently used antihypertensive medications with additional advantages such as reducing proteinuria and cardiovascular events. ACEi are commonly held at least 24 hours before a therapeutic plasma exchange (TPE) to reduce possibility of adverse events (AEs) including adverse drug reactions (ADR). The objective of this study was to determine if ACEi use increases the risk of ADR in patients receiving TPE with a conventional centrifuge-based apheresis system. This is a retrospective chart review study (n = 252; 52% male). Binary logistic regression was used to analyze the association of ACEi use and AEs. Of 171 patients who had AE during TPE, only 38 patients were taking ACEi. There was no significant association between ACEi use and AEs after adjustments (odds ratio = 0.885, 95% confidence interval: 0.468, 1.674). Our results suggest that risk of AEs is not higher in patients taking ACEi receiving TPE using a centrifuge-based machine. Randomized controlled prospective trials may be needed to further investigate this matter.

IGF-1 Deficiency Rescue and Intracellular Calcium Blockade Improves Survival and Corresponding Mechanisms in a Mouse Model of Acute Kidney Injury.

This study was undertaken to test two therapies for acute kidney injury (AKI) prevention, IGF-1, which is renal protective, and BTP-2, which is a calcium entry (SOCE) inhibitor. We utilized lipopolysaccharide (LPS) IP, as a systemic model of AKI and studied in five groups of animals. Three experiments showed that at 7 days: (1) LPS significantly reduced serum IGF-1 and intramuscular IGF-I in vivo gene therapy rescued this deficiency. (2) Next, at the 7-day time point, our combination therapy，compared to the untreated group,caused a significant increase in survival, which was noteworthy because all of the untreated animals died in 72 hrs. (3) The four pathways associated with inflammation, including (A) increase in cytosolic calcium, (B) elaboration of proinflammatory cytokines, (C) impairment of vascular integrity, and (D) cell injury, were adversely affected in renal tissue by LPS, using a sublethal dose of LPS. The expression of several genes was measured in each of the above pathways. The combined therapy of IGF-1 and BTP-2 caused a favorable gene expression response in all four pathways. Our current study was an AKI study, but these pathways are also involved in other types of severe inflammation, including sepsis, acute respiratory distress syndrome, and probably severe coronavirus infection.

Red blood cell exchange in treatment of severe cerebral P. falciparum malaria: A case report.

INTRODUCTION: Red blood cells exchange transfusion has been demonstrated to be helpful in treatment of sever P. falciparum malaria. However, no large scale randomized controlled trials have been completed to date and the CDC does not recommend RBC exchange transfusions as standard of care. We present a case of severe cerebral malaria in a patient with extremely high parasitemia and severe altered mental status who improved rapidly with automated RBC exchange. REPORT: Seventy-two year old female presented with 1 day history of weakness, altered mental status, malaise, and cyclic sweats after returning from a trip to Sierra Leone. Thick and Thin Smears demonstrated P. falciparum rings present and Quantitative malaria screen demonstrated 53.33% parasitemia. Patient was started on quinidine and doxycycline but continued to deteriorate. Automated RBC exchange transfusion was performed within 24 hours of admission and resulted in rapid improvement in symptomology. Repeat thick and thin smears revealed undetectable parasite load. CONCLUSION: Automated RBC exchange may improve outcomes in severe P. falciparum malaria when presenting parasite loads are very high.