Successful management of concurrent COVID-19 and Pneumocystis Jirovecii Pneumonia in kidney transplant recipients: a case series

Abstract Background Pneumocystis pneumonia (PCP) is a life-threatening pulmonary fungal infection that predominantly affects immunocompromised individuals, including kidney transplant recipients. Recent years have witnessed a rising incidence of PCP in this vulnerable population, leading to graft loss and increased mortality. Immunosuppression, which is essential in transplant recipients, heightens susceptibility to viral and opportunistic infections, magnifying the clinical challenge. Concurrently, the global impact of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been profound. Kidney transplant recipients have faced severe outcomes when infected with SARS-CoV-2, often requiring intensive care. Co-infection with COVID-19 and PCP in this context represents a complex clinical scenario that requires precise management strategies, involving a delicate balance between immunosuppression and immune activation. Although there have been case reports on management of COVID-19 and PCP in kidney transplant recipients, guidance on how to tackle these infections when they occur concurrently remains limited. Case presentations We have encountered four kidney transplant recipients with concurrent COVID-19 and PCP infection. These patients received comprehensive treatment that included adjustment of their maintenance immunosuppressive regimen, anti-pneumocystis therapy, treatment for COVID-19 and other infections, and symptomatic and supportive care. After this multifaceted treatment strategy, all of these patients improved significantly and had favorable outcomes. Conclusions We have successfully managed four kidney transplant recipients co-infected with COVID-19 and PCP. While PCP is a known complication of immunosuppressive therapy, its incidence in patients with COVID-19 highlights the complexity of dual infections. Our findings suggest that tailored immunosuppressive regimens, coupled with antiviral and antimicrobial therapies, can lead to clinical improvement in such cases. Further research is needed to refine risk assessment and therapeutic strategies, which will ultimately enhance the care of this vulnerable population

Assessment of Urinary Exosomal NHE3 as a Biomarker of Acute Kidney Injury

The diagnosis of acute kidney injury (AKI) traditionally depends on the serum creatinine (Scr) and urine output, which lack sufficient sensitivity and specificity. Using urinary exosomes as a biomarker has unique advantages. To assess whether urinary exosomal Na+/H+ exchanger isoform 3 (NHE3) protein could serve as a biomarker of AKI, we constructed four AKI rat models: cisplatin (7.5 mg/kg) injected intraperitoneally (IP), furosemide (20 mg/kg, IP) with a low-NaCl (0.03%) diet, a low-NaCl (0.03%) diet with candesartan (1 mg/kg, IP) and bilateral ischemia and reperfusion (I/R) injury for 40 min. Additionally, we assessed six sepsis-associated AKI patients and six healthy volunteers. Urinary exosomes were extracted by ultracentrifugation, and the NHE3 protein abundance was tested by immunoblotting for all the AKI rats and human subjects. The isolated cup-shaped particles with an average diameter of 70 nm and enrichment in CD63 were identified as exosomes. NHE3 abundance was six times higher in exosomes than in the whole urine. In cisplatin-induced AKI rats, urinary exosomal NHE3 was increased on day 2, one day earlier than the increases in Scr and blood urea nitrogen (BUN). In additional rats, urinary exosomal NHE3 decreased along with the decline in Scr after EPO pretreatment. In volume-depletion AKI induced by furosemide injection with a low-NaCl diet, the urinary exosomal NHE3 expression was higher than that in the control. Under a low-NaCl diet with candesartan-related AKI, the urinary exosomal NHE3 was elevated on day 5, earlier than Scr. In I/R-injury AKI, the urinary exosomal NHE3 was also raised compared with that in the control. In humans, the urinary exosomal NHE3 level was also elevated in sepsis-associated AKI patients in comparison with that in the healthy volunteers. The urinary exosomal NHE3 was increased in multiple AKI; it may be used as a diagnostic biomarker of AKI

Decreased Platelet Count in Patients Receiving Continuous Veno-Venous Hemofiltration: A Single-Center Retrospective Study

<div><p>Background</p><p>A decreased platelet count may occur and portend a worse outcome in patients receiving continuous renal replacement therapy (CRRT). We aim to investigate the incidence of decreased platelet count and related risk factors in patients receiving CRRT.</p><p>Methods</p><p>In this retrospective study, we screened all patients receiving continuous veno-venous hemofiltration (CVVH) at Jinling Hospital between November 2008 and October 2012. The patients were included who received uninterrupted CVVH for more than 72 h and had records of blood test for 4 consecutive days after ruling out pre-existing conditions that may affect the platelet count. Platelet counts before and during CVVH, illness severity, CVVH settings, and outcomes were analyzed.</p><p>Results</p><p>The study included 125 patients. During the 3-day CVVH, 44.8% and 16% patients had a mild decline (20–49.9%) and severe decline (≥50%) in the platelet count,respectively; 37.6% and 16.0% patients had mild thrombocytopenia (platelet count 50.1–100×10⁹/L) and severe thrombocytopenia (platelet count ≤50×10⁹/L), respectively. Patients with a severe decline in the platelet count had a significantly lower survival rate than patients without a severe decline in the platelet count (35.0% versus 59.0%, P = 0.012), while patients with severe thrombocytopenia had a survival rate similar to those without severe thrombocytopenia (45.0% versus 57.1%, P = 0.308). Female gender, older age, and longer course of the disease were independent risk factors for a severe decline in the platelet count.</p><p>Conclusions</p><p>A decline in the platelet count and thrombocytopenia are quite common in patients receiving CVVH. The severity of the decline in the platelet count rather than the absolute count during CVVH may be associated with hospital mortality. Knowing the risk factors for a severe decline in the platelet count may allow physicians to prevent such an outcome.</p></div

Univariate and multivariate adjusted Cox regression analyses of risk factors for mortality.

<p>Adjusted factor is gender. APACHE: acute physiology and chronic health Evaluation; SOFA: sequential organ failure assessment.</p

Multivariate analyses of independent risk factors for a severe decline in the platelet count and severe thrombocytopenia during 3-day continuous veno-venous hemofiltration.

<p>Adjusted factors include age, gender, APACHE II score, SOFA score, sepsis, hypotension, times of hemofilter clotting, anticoagulation, blood flow, dose, course of the disease and thrombocytopenia before CVVH. APACHE: acute physiology and chronic health Evaluation; AUROC: area under the receiver operating characteristic curve; CVVH: continuous veno-venous hemofiltration; OR = odds ratio.</p

Kaplan-Meier plots for cumulative 90-day survival.

<p>Patients with a severe decline in the platelet count (≥50%) in 3-day CVVH had a worse 90-day survival than those with a mild decline in the platelet count (20–49.9%) or with no decline in the platelet count (<20%; Figure 2A). Patients with severe thrombocytopenia (Lowest Platelet count ≤50×10⁹/L) in 3-day CVVH had a similar 90-day survival compared to those with mild thrombocytopenia (Lowest Platelet count 50.1–100×10⁹/L) or with normal platelet counts (Lowest Platelet count>100×10⁹/L; Figure 2B). CVVH: continuous veno-venous hemofiltration.</p

Flow chart of study participation.

<p>DIC: disseminated intravascular coagulation; DIT: drug-induced thrombocytopenia; SLE: systemic lupus erythematosus; EC: extracorporeal circulation; ECMO: extracorporeal membrane oxygenation; MARS: molecular adsorbent recirculating system.</p

The change in the platelet count and associated parameters and during continuous veno-venous hemofiltration (n = 125).

<p>*P<0.05 compared with pre-CVVH. CVVH: continuous veno-venous hemofiltration; PCs: platelet counts.</p

Baseline characteristics of the study population.

<p>APACHE: acute physiology and chronic health Evaluation; AKI: Acute kidney injury; CRRT: continuous renal replacement therapy; MPV: mean platelet volume; PCs: platelet counts; SOFA: sequential organ failure assessment; SIRS: systemic inflammatory reaction syndrome.</p><p>*P<0.05 compared with PCs reduction ≥50%;</p>†<p>P<0.01 compared with PCs reduction ≥50%.</p