Comparison of hospitalization outcomes for delivery and resource utilization between pregnant women with kidney transplants and chronic kidney disease in the United States.

BACKGROUND: This study aimed to assess outcomes of delivery hospitalizations, including acute kidney injury (AKI), obstetric and foetal events and resource utilization among pregnant women with kidney transplants compared with pregnant women with no known kidney disease and those with chronic kidney disease (CKD) Stages 3-5. METHOD: Hospitalizations for delivery in the US were identified using the enhanced delivery identification method in the National Inpatient Sample dataset from the years 2009 to 2014. Diagnoses of CKD Stages 3-5, kidney transplantation, along with obstetric events, delivery methods and foetal events were identified using ICD-9-CM diagnosis and procedure codes. Patients with no known kidney disease group were identified by excluding any diagnoses of CKD, end stage kidney disease, and kidney transplant. Multivariable logistic regression accounting for the survey weights and matched regression was conducted to investigate the risk of maternal and foetal complications in women with kidney transplants, compared with women with no kidney transplants and no known kidney disease, and to women with CKD Stages 3-5. RESULT: A total of 5, 408, 215 hospitalizations resulting in deliveries were identified from 2009 to 2014, including 405 women with CKD Stages 3-5, 295 women with functioning kidney transplants, and 5, 405, 499 women with no known kidney disease. Compared with pregnant women with no known kidney disease, pregnant kidney transplant recipients were at higher odds of hypertensive disorders of pregnancy (OR = 3.11, 95% CI [2.26, 4.28]), preeclampsia/eclampsia/HELLP syndrome (OR = 3.42, 95% CI [2.54, 4.60]), preterm delivery (OR = 2.46, 95% CI [1.75, 3.45]), foetal growth restriction (OR = 1.74, 95% CI [1.01, 3.00]) and AKI (OR = 10.46, 95% CI [5.33, 20.56]). There were no significant differences in rates of gestational diabetes or caesarean section. Pregnant women with kidney transplants had 1.30-times longer lengths of stay and 1.28-times higher costs of hospitalization. However, pregnant women with CKD Stages 3-5 were at higher odds of AKI (OR = 5.29, 95% CI [2.41, 11.59]), preeclampsia/eclampsia/HELLP syndrome (OR = 1.72, 95% CI [1.07, 2.76]) and foetal deaths (OR = 3.20, 95% CI [1.06, 10.24]), and had 1.28-times longer hospital stays and 1.37-times higher costs of hospitalization compared with pregnant women with kidney transplant. CONCLUSION: Pregnant women with kidney transplant were more likely to experience adverse events during delivery and had longer lengths of stay and higher total charges when compared with women with no known kidney disease. However, pregnant women with moderate to severe CKD were more likely to experience serious complications than kidney transplant recipients.

The sensitivity and specificity of the routine kidney biopsy immunofluorescence panel are inferior to diagnosing renal immunoglobulin-derived amyloidosis by mass spectrometry.

Immunoglobulin light chain amyloidosis is the most frequent type of renal amyloidosis in the United States, accounting for 81% of cases. Accurate typing is crucial for early diagnosis and treatment of immunoglobulin-derived amyloidosis and to avoid treating other amyloidoses with potentially toxic chemotherapy. Immunofluorescence is the first step to type renal immunoglobulin-derived amyloidosis but the performance characteristics of this method are largely unknown. Here, we establish the sensitivity and specificity of immunofluorescence for diagnosing immunoglobulin-derived amyloidosis in patients whose amyloid typing was performed by the current gold standard of laser microdissection/mass spectrometry. Renal biopsy pathology reports originating from several institutions with a diagnosis of amyloidosis and which had amyloid typing by laser microdissection/mass spectrometry performed at our center were reviewed. Reported immunofluorescence staining for kappa or lambda of 2+ or more, with weak or no staining for the other light chain was considered positive for light chain amyloidosis by immunofluorescence. Based on microdissection/mass spectrometry results, of the 170 cases reviewed, 104 cases were typed as immunoglobulin-derived amyloidosis and 66 were typed as non-immunoglobulin-derived amyloidosis. Immunofluorescence sensitivity for diagnosing immunoglobulin-derived amyloidosis was 84.6%. The remaining 16 cases could not be diagnosed by immunofluorescence due to reported weak staining for all antigens or reported lack of preferential staining for one antigen. Immunofluorescence specificity was 92.4%. Five cases, all amyloid A amyloidosis, were misdiagnosed as immunoglobulin-derived amyloidosis by immunofluorescence. Immunofluorescence failed to accurately differentiate immunoglobulin-derived from non-immunoglobulin-derived amyloidosis in 12.3% of cases of renal amyloidosis. Relying on immunofluorescence alone for determining immunoglobulin-derived vs. non-immunoglobulin-derived amyloidosis may lead to misdiagnosis. Thus, immunofluorescence has inferior sensitivity and specificity compared with laser microdissection/mass spectrometry in the typing of immunoglobulin-derived amyloidosis.

Renal Disorders in Pregnancy: Core Curriculum 2019.

As the incidence of chronic kidney disease increases and women pursue pregnancy at more advanced ages, the management of kidney disease in pregnancy has become increasingly relevant to the practicing nephrologist. Women with kidney disorders face several challenges in pregnancy due to increased physiologic demands on the kidney and risk for disease progression, the potential teratogenicity of medications, and the increased risk for complications such as preeclampsia and preterm delivery. Challenges posed by an underlying disease process in pregnancy, such as autoimmune disease or diabetes mellitus, necessitate an interdisciplinary team to ensure good maternal and fetal outcomes. Rates of acute kidney injury in pregnancy are generally declining worldwide, but remain a significant public health concern in developing countries. Pregnancy may also be the first time that a woman has kidney disease or hypertension diagnosed. An understanding of what constitutes normal physiologic changes in pregnancy is critical in a diagnostic evaluation. In this review, we review physiologic changes in pregnancy, causes and management of acute kidney injury in pregnancy, hypertensive disorders of pregnancy, and how to care for women with chronic kidney disease of various causes, including the use of antihypertensives and immunosuppressants.

Association between urologic malignancies and end-stage renal disease: A meta-analysis.

AIM: Previous studies have suggested a higher incidence of urologic malignancies in end-stage renal disease (ESRD) patients. However, incidence trends of urologic malignancies in ESRD patients remain unclear. The aims of the present study were: (i) to investigate the pooled incidence/incidence trends; and (ii) to assess the risk of urologic malignancies in ESRD patients. METHODS: A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through April 2017. Studies that reported incidence or odds ratios of urologic malignancies among ESRD patients were included. Pooled odds ratios (OR) and 95%CI were calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017067687). RESULTS: Nineteen observational studies with 1 931 073 ESRD patients were enrolled. The pooled estimated incidence of kidney cancer and urothelial cancers (carcinomas of the bladder, ureters, and renal pelvis) in ESRD patients were 0.3% (95%CI: 0.2-0.5%) and 0.5% (95%CI: 0.3-0.8%), respectively. Meta-regression showed significant positive correlation between incidence of urologic malignancies in ESRD patients and year of study (slopes = +0.05 and +0.07, P < 0.001 for kidney cancer and urothelial cancers, respectively). Compared to non-ESRD status, ESRD was significantly associated with both kidney cancer (pooled OR 6.04; 95% CI 4.70-7.77) and urothelial cancers (pooled OR 4.37; 95% CI 2.40-7.96). CONCLUSION: Our study demonstrates a significant association between ESRD and urologic malignancies. The overall estimated incidence rates of kidney cancer and urothelial cancers are 0.4% and 0.5%, respectively. There is a significant positive correlation between the incidence of urologic malignancies and year of study.

Longitudinal characterization of renal proximal tubular markers in normotensive and preeclamptic pregnancies.

Glomerular damage is common in preeclampsia (PE), but the extent and etiology of tubular injury are not well understood. The aim of this study was to evaluate tubular injury in patients with PE and to assess whether it predates clinical disease. We performed a prospective cohort study of 315 pregnant women who provided urine samples at the end of the second trimester and at delivery. This analysis included women who developed PE (n = 15), gestational hypertension (GH; n = 14), and normotensive controls (NC; n = 44). Urinary markers of tubular injury, α1-microglobulin (A1M), retinol-binding protein (RBP), kidney-injury molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine creatinine concentration. Second-trimester concentrations of all markers were similar among groups. At delivery, A1M concentrations were higher in the PE group than in the GH and NC groups as an A1M/creatinine ratio >13 (66.7, 8.3, and 35%, respectively, P = 0.01). Concentrations of C5b-9 were higher in the PE group than in the GH and NC groups (medians 9.85, 0.05, and 0.28 ng/mg, respectively, P = 0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and C5b-9, developed during the interval between the end of the second trimester and delivery in patients with PE. However, this was not matched by abnormalities in markers previously associated with tubular cell injury (KIM-1, IGFBP-7, and TIMP-2).

The effects of short sleep duration on proteinuria and chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: The risks of proteinuria and chronic kidney disease (CKD) in adults who regularly have short sleep duration (short sleepers) are controversial. The aim of this meta-analysis was to assess the effects of short sleep duration on proteinuria and CKD. METHODS: A literature search was conducted using MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from the inception of the databases through November 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risks of proteinuria and CKD in short sleepers were included. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed utilizing a random-effect, generic inverse variance method. RESULTS: Six observational studies with 252 075 individuals and three observational studies with 37 197 individuals were included in the analyses to assess the risks of CKD and proteinuria in short sleepers, respectively. The pooled RR of CKD in short sleepers was 1.51 (95% CI, 0.99-2.55). When meta-analysis was restricted only to studies with adjusted analysis for confounders assessing the risk of CKD in short sleepers, the pooled RR of CKD was 1.54 (95% CI, 0.80-2.95). The pooled RR of proteinuria in short sleepers was 1.47 (95% CI, 1.26-1.72). CONCLUSIONS: Despite the lack of significant association between short sleep duration and CKD, our meta-analysis suggests a potential association between short sleep duration and proteinuria, a surrogate marker for kidney disease progression. Future study is required to investigate if reversal of short sleep helps reduce proteinuria.

Transforming Healthcare: The AI Revolution in the Comprehensive Care of Hypertension.

This review explores the transformative role of artificial intelligence (AI) in hypertension care, summarizing and analyzing published works from the last three years in this field. Hypertension contributes to a significant healthcare burden both at an individual and global level. We focus on five key areas: risk prediction, diagnosis, education, monitoring, and management of hypertension, supplemented with a brief look into the works on hypertensive disease of pregnancy. For each area, we discuss the advantages and disadvantages of integrating AI. While AI, in its current rudimentary form, cannot replace sound clinical judgment, it can still enhance faster diagnosis, education, prevention, and management. The integration of AI in healthcare is poised to revolutionize hypertension care, although careful implementation and ongoing research are essential to mitigate risks.

AI-driven translations for kidney transplant equity in Hispanic populations.

Health equity and accessing Spanish kidney transplant information continues being a substantial challenge facing the Hispanic community. This study evaluated ChatGPT's capabilities in translating 54 English kidney transplant frequently asked questions (FAQs) into Spanish using two versions of the AI model, GPT-3.5 and GPT-4.0. The FAQs included 19 from Organ Procurement and Transplantation Network (OPTN), 15 from National Health Service (NHS), and 20 from National Kidney Foundation (NKF). Two native Spanish-speaking nephrologists, both of whom are of Mexican heritage, scored the translations for linguistic accuracy and cultural sensitivity tailored to Hispanics using a 1-5 rubric. The inter-rater reliability of the evaluators, measured by Cohen's Kappa, was 0.85. Overall linguistic accuracy was 4.89 ± 0.31 for GPT-3.5 versus 4.94 ± 0.23 for GPT-4.0 (non-significant p = 0.23). Both versions scored 4.96 ± 0.19 in cultural sensitivity (p = 1.00). By source, GPT-3.5 linguistic accuracy was 4.84 ± 0.37 (OPTN), 4.93 ± 0.26 (NHS), 4.90 ± 0.31 (NKF). GPT-4.0 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 4.95 ± 0.22 (NKF). For cultural sensitivity, GPT-3.5 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 5.00 ± 0.00 (NKF), while GPT-4.0 scored 5.00 ± 0.00 (OPTN), 5.00 ± 0.00 (NHS), 4.90 ± 0.31 (NKF). These high linguistic and cultural sensitivity scores demonstrate Chat GPT effectively translated the English FAQs into Spanish across systems. The findings suggest Chat GPT's potential to promote health equity by improving Spanish access to essential kidney transplant information. Additional research should evaluate its medical translation capabilities across diverse contexts/languages. These English-to-Spanish translations may increase access to vital transplant information for underserved Spanish-speaking Hispanic patients.

Divergent changes in PBN excitability in a mouse model of neuropathic pain.

The transition from acute to chronic pain involves maladaptive plasticity in central nociceptive pathways. Growing evidence suggests that changes within the parabrachial nucleus (PBN), an important component of the spino-parabrachio-amygdaloid pain pathway, are key contributors to the development and maintenance of chronic pain. In animal models of chronic pain, PBN neurons become sensitive to normally innocuous stimuli and responses to noxious stimuli become amplified and more often produce after-discharges that outlast the stimulus. Using ex vivo slice electrophysiology and two mouse models of neuropathic pain, sciatic cuff and chronic constriction of the infraorbital nerve (CCI-ION), we find that changes in the firing properties of PBN neurons and a shift in inhibitory synaptic transmission may underlie this phenomenon. Compared to PBN neurons from shams, a larger proportion of PBN neurons from mice with a sciatic cuff were spontaneously active at rest, and these same neurons showed increased excitability relative to shams. In contrast, quiescent PBN neurons from cuff mice were less excitable than those from shams. Despite an increase in excitability in a subset of PBN neurons, the presence of after-discharges frequently observed in vivo were largely absent ex vivo in both injury models. However, GABAB-mediated presynaptic inhibition of GABAergic terminals is enhanced in PBN neurons after CCI-ION. These data suggest that the amplified activity of PBN neurons observed in rodent models of chronic pain arise through a combination of changes in firing properties and network excitability.Significance Statement Hyperactivity of neurons in the parabrachial nucleus (PBN) is causally linked to exaggerated pain behaviors in rodent models of chronic pain but the underlying mechanisms remain unknown. Using two mouse models of neuropathic pain, we show the intrinsic properties of PBN neurons are largely unaltered following injury. However, subsets of PBN neurons become more excitable and GABAB receptor mediated suppression of inhibitory terminals is enhanced after injury. Thus, shifts in network excitability may be a contributing factor in injury induced potentiation of PBN activity.

Comparable outcomes of outpatient remdesivir and sotrovimab among high-risk patients with mild to moderate COVID-19 during the omicron BA.1 surge.

Studies conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness has not been directly compared. This study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups. Among 3257 patients, 2158 received sotrovimab and 1099 received remdesivir. Patients treated with sotrovimab were younger and had lower comorbidity but were more likely to be immunocompromised than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine. COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab, respectively, p = .15) and mortality within 28 days (0.4% in both groups, p = .82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the outcomes between the two groups. We demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab.

The parabrachial to central amygdala pathway is critical to injury-induced pain sensitization in mice.

The spino-ponto-amygdaloid pathway is a major ascending circuit relaying nociceptive information from the spinal cord to the brain. Potentiation of excitatory synaptic transmission in the parabrachial nucleus (PBN) to central amygdala (CeA) pathway has been reported in rodent models of persistent pain. However, the functional significance of this pathway in the modulation of the somatosensory component of pain was recently challenged by studies showing that spinal nociceptive neurons do not target CeA-projecting PBN cells and that manipulations of this pathway have no effect on reflexive-defensive somatosensory responses to peripheral noxious stimulation. Here, we showed that activation of CeA-projecting PBN neurons is critical to increase both stimulus-evoked and spontaneous nociceptive responses following an injury in male and female mice. Using optogenetic-assisted circuit mapping, we confirmed a functional excitatory projection from PBN→CeA that is independent of the genetic or firing identity of CeA cells. We then showed that peripheral noxious stimulation increased the expression of the neuronal activity marker Fos in CeA-projecting PBN neurons and that chemogenetic inactivation of these cells decreased behavioral hypersensitivity in models of neuropathic and inflammatory pain without affecting baseline nociception. Lastly, we showed that chemogenetic activation of CeA-projecting PBN neurons is sufficient to induced bilateral hypersensitivity without injury. Together, our results indicate that the PBN→CeA pathway is a key modulator of pain-related behaviors that can increase reflexive-defensive and affective-motivational responses to somatosensory stimulation in injured states without affecting nociception under normal physiological conditions.

GABA release from central amygdala neurotensin neurons differentially modulates ethanol consumption in male and female mice.

The central nucleus of the amygdala is known to play key roles in alcohol use and affect. Neurotensin neurons in the central nucleus of the amygdala have been shown to regulate alcohol drinking in male mice. However, little is known about which neurotransmitters released by these cells drive alcohol consumption or whether these cells drive alcohol consumption in female mice. Here we show that knockdown of GABA release from central amygdala neurotensin neurons using a Nts-cre-dependent vGAT-shRNA-based AAV strategy reduces alcohol drinking in male, but not female, mice. This manipulation did not impact avoidance behavior, except in a fasted novelty-suppressed feeding test, in which vGAT shRNA mice demonstrated increased latency to feed on a familiar high-value food reward, an effect driven by male mice. In contrast, vGAT shRNA female mice showed heightened sensitivity to thermal stimulation. These data show a role for GABA release from central amygdala neurotensin neurons in modulating consumption of rewarding substances in different motivational states.

Divergent changes in PBN excitability in a mouse model of neuropathic pain.

The transition from acute to chronic pain involves maladaptive plasticity in central nociceptive pathways. Growing evidence suggests that changes within the parabrachial nucleus (PBN), an important component of the spino-parabrachio-amygdaloid pain pathway, are key contributors to the development and maintenance of chronic pain. In animal models of chronic pain, PBN neurons become sensitive to normally innocuous stimuli and responses to noxious stimuli become amplified and more often produce after-discharges that outlast the stimulus. Using ex vivo slice electrophysiology and two mouse models of neuropathic pain, sciatic cuff and chronic constriction of the infraorbital nerve (CCI-ION), we find that changes in the firing properties of PBN neurons and a shift in inhibitory synaptic transmission may underlie this phenomenon. Compared to PBN neurons from shams, a larger proportion of PBN neurons from mice with a sciatic cuff were spontaneously active at rest, and these same neurons showed increased excitability relative to shams. In contrast, quiescent PBN neurons from cuff mice were less excitable than those from shams. Despite an increase in excitability in a subset of PBN neurons, the presence of after-discharges frequently observed in vivo were largely absent ex vivo in both injury models. However, GABAB-mediated presynaptic inhibition of GABAergic terminals is enhanced in PBN neurons after CCIION. These data suggest that the amplified activity of PBN neurons observed in rodent models of chronic pain arise through a combination of changes in firing properties and network excitability.

GABA Release From Central Amygdala Neurotensin Neurons Differentially Modulates Reward and Consummatory Behavior in Male and Female Mice.

The central nucleus of the amygdala is known to play key roles in alcohol use and affect. Neurotensin neurons in the central nucleus of the amygdala have been shown to regulate alcohol drinking in male mice. However, little is known about which neurotransmitters released by these cells drive alcohol consumption or whether these cells drive alcohol consumption in female mice. Here we show that knockdown of GABA release from central amygdala neurotensin neurons using a Nts-cre-dependent vGAT-shRNA-based AAV strategy reduces alcohol drinking in male, but not female, mice. This manipulation did not impact avoidance behavior, except in a fasted novelty-suppressed feeding test, in which vGAT shRNA mice demonstrated increased latency to feed on a familiar high-value food reward, an effect driven by male mice. In contrast, vGAT shRNA female mice showed heightened sensitivity to thermal stimulation. These data show a role for GABA release from central amygdala neurotensin neurons in modulating consumption of rewarding substances in different motivational states.

Quantitative Alterations in Complement Alternative Pathway and Related Genetic Analysis in Severe Phenotype Preeclampsia.

Background: Preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome share many clinical and biologic features with thrombotic microangiopathy syndromes caused by complement abnormalities. Our hypothesis was that similar functional and genetic alterations in the complement alternative pathway (CAP) are present in these disorders of pregnancy. Methods: We conducted quantitative analysis of proteins involved in CAP using ELISA and nephelometry on prospectively collected blood samples from patients with severe phenotype preeclampsia (defined as delivery ≤34 weeks due to preeclampsia), HELLP syndrome, or eclampsia, and matched normotensive controls (n=25 in each arm) between 2011 and 2016. Sequencing was performed to interrogate 14 genes encoding CAP components. Results: Both groups were similar in age, gravidity, parity, marital status, and race. The study group had a higher BMI (mean±SD, 32±8 versus 25±4 kg/m2; P=0.002) and earlier gestational age at delivery (32.5±3.6 versus 40.3±1 weeks; P<0.001). Serologic studies demonstrated elevated Bb subunit (median [range], 1.2 [0.5-4.3] versus 0.6 [0.5-1] µg/ml; P<0.001), complement C5 concentration (28 [18-33] versus 24 [15-34] mg/dl; P=0.03), and sMAC (371 [167-761] versus 184 [112-249] ng/ml; P<0.001) concentrations in patients with preeclampsia. Two thirds of patients with preeclampsia had at least one nonsynonymous sequence variant in CAP genes. Conclusion: Patients with severe phenotype preeclampsia manifest functional alterations in CAP activation. Genetic variants in the CAP genes were detected in several patients, but a larger population study is necessary to fully evaluate genetic risk. Genetic screening and complement-targeted treatment may be useful in risk stratification and novel therapeutic approaches.

Xanthine nephrolithiasis in a galician blond beef calf.

A six-month-old female Galician Blond beef calf presented signs of apathy, anorexia and weight loss. The analysis of a blood sample confirmed renal failure. Bilateral nephrolithiasis was diagnosed at necropsy. Quantitative analysis revealed the nephroliths to be composed of 100 per cent xanthine. In cattle, xanthinuria has only been described in the Japanese Black breed, but never before in other breeds. Clinical history suggested a naturally occurring xanthinuria.

Pregnancy in Kidney Transplant Recipients.

Women with end-stage kidney disease commonly have difficulty conceiving through spontaneous pregnancy, and many suffer from infertility. Kidney transplantation restores the impairment in fertility and increases the possibility of pregnancy. In addition, the number of female kidney transplant recipients of reproductive age has been increasing. Thus, preconception counseling, contraceptive management, and family planning are of great importance in the routine care of this population. Pregnancy in kidney transplant recipients is complicated by underlying maternal comorbidities, kidney allograft function, the effect of pregnancy on the transplanted kidney, and the effect of the maternal health on the fetus, in addition to immunosuppressive medications and their potential teratogenesis. Given the potential maternal and fetal risks, and possible complications during pregnancy, pretransplant and prepregnancy counseling for women of reproductive age are crucial, including delivery of information regarding contraception and timing for pregnancy, fertility and pregnancy rates, the risk of immunosuppression on the fetus, the risk of kidney allograft, and other maternal complications. In this article, we discuss aspects related to pregnancy among kidney transplant recipients and their management.

Serological evaluation of selected vector-borne pathogens in owned dogs from northern Spain based on a multicenter study using a commercial test.

BACKGROUND: Environmental conditions in northern Spain allow the development of different arthropods involved in the transmission of significant canine vector-borne pathogens. The aim of the study was to systematically assess seroprevalence rates for Leishmania infantum, Ehrlichia canis, Anaplasma spp., Dirofilaria immitis and Borrelia burgdorferi, and risk factors in dogs from all regions of the north of Spain. METHODS: A total of 556 dogs were included in this study between January 2017 and December 2018, belonging to 30 practices covering all regions in northern Spain (Galicia, Asturias, Cantabria, Basque Country, Navarra, Aragon and Catalonia). All practices were located in the north of every region. Blood samples were analyzed using the 4DX SNAP® test (IDEXX Laboratories, Westbrook, Maine, USA) for the detection of D. immitis antigen and E. canis, B. burgdorferi and Anaplasma spp. antibodies. Leishmania SNAP® test (IDEXX Laboratories) was used for detection of L. infantum antibodies. Associations between prevalence of canine vector-borne pathogens, epidemiological and clinical signs data were statistically analyzed. RESULTS: The overall prevalence rates were 8.99% for L. infantum, 1.26% for Anaplasma spp., 0.9% for E. canis, 0.72% for B. burgdorferi, and 0.18% for D. immitis. Globally, 11.33% of the dogs included in the study were positive to any tested vector-borne pathogen. Leishmania infantum seroprevalence was the highest and the only one detected in all the regions. Leishmania infantum seropositivity was associated with age > 10 years-old, outdoor access, anemia, fever, dermatological signs, lympadenomegaly, muscular atrophy, ocular signs and renal disease. Ehrlichia canis seropositivity was associated with the summer season and living in urban areas. Apathy, weakness, anorexia, weight loss, anemia, fever and gastrointestinal clinical signs were also associated with E. canis antibody detection. Living in a rural area was also a risk factor for Anaplasma spp. and B. burgdorferi seropositivity. CONCLUSIONS: To our knowledge, this is the first multicenter survey performed in northern Spain assessing different canine vector-borne diseases from all regions. Results show the presence of autochthonous cases of these diseases. The vector-borne pathogens found in this study should be included in the differential diagnosis in dogs from some areas previously considered non-endemic for these pathogens.

Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review.

BACKGROUND: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx. METHODS: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718). RESULTS: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12-57%) after eculizumab, 42% (95% CI: 2-89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50-100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5-46%) after eculizumab, 56% (95% CI: 6-100%) after TPE, and 70% (95% CI: 24-100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0-100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7-64%) and 53% (95% CI: 28-77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). 80% of patients with elevated sMAC before eculizumab responded to treatment. In addition, all patients who responded to eculizumab had normal sMAC levels after post-eculizumab. CONCLUSIONS: Our study suggests that the lowest incidence of allograft loss (33%) among KTX patients with C3G are those treated with eculizumab. Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.

Outcomes of Kidney Transplantation in Fabry Disease: A Meta-Analysis.

BACKGROUND: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD. METHODS: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. RESULTS: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%-42.5%), 14.5% (95%CI: 8.4%-23.7%), and 20.2% (95%CI: 15.4%-25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%-37.3%), 11.7% (95%CI: 8.4%-16.0%), and 20.2% (95%CI: 15.5%-26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%-29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD. CONCLUSIONS: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.