Tuesday, September 1, 2020

Topic Discussion: Gut Microbiota and UTIs

 


A Gut Microbiota – Urinary Tract Infection Connection

It is presumed that gut bacteria are the source for urinary tract infection, but is there any proof? If so, could changing the gut microbiota impact urinary tract infection?

Lee et al. evaluated this premise in a cohort of 168 kidney transplant recipients and profiled the gut microbiota serially using 16S rRNA deep sequencing. They reported that having higher gut abundance of E. coli was a risk factor for development of E. coli. They further performed strain analysis on matched fecal-urine specimens and found that the E. coli in the urine most closely resemble the E. coli in the gut from the same patients, supporting a gut origin of UTIs .

A follow up analysis identified that the gut abundances of two commensal bacteria, Faecalibacterium and Romboutsia, are associated with a decreased risk for UTIs

The data suggest the possibility that manipulation of the gut microbiota could alter the balance of commensal bacteria and pathogenic bacteria and could decrease the risk of UTIs, especially in patients with recurrent UTIs. Indeed, there is some recent evidence in case reports. In a case series by Tariq et al., patients with recurrent UTIs and recurrent C. difficile infections underwent fecal microbial transplantation for recurrent C. difficile infections and had a significant decrease in the number of UTIs after fecal microbial transplantation.

Whether gut microbial-based therapies can break the cycle of recurrent UTIs is still not known. Nevertheless, these therapies could be a novel approach to treating this common problem.


Image credit: http://www.sci-news.com/biology/gut-microbiota-manipulate-our-minds-05956.html

Thursday, August 20, 2020

Topic Discussion: ESRD patients and COVID-19


Kidneys And Covid-19: Renal Manifestations Of The Novel Coronavirus

While we saw several rising cases of AKI associated with COVID-19, the ESKD population was also vulnerable to this virus. With COVID-19, we didn't know if we would see worsening effects on ESRD or beneficial ( given a not so robust immune system in ESRD).  But the proximity and being in a closed dialysis unit did put most of them at risk. 

Studies from China and Europe on ESKD patients with COVID-19 were limited to small numbers and single centers. One of the first studies from US from CUMC was limited by less then 100 patients as well. It did show poor outcomes of 59 patients where 31% had died.


A Study from UK did discuss the concerns for an urban dialysis center ( on risk of hospitalizations). Of 1530 patients (median age 66 years; 58.2% men) receiving dialysis, 300 (19.6%) developed COVID-19 infection, creating a large demand for isolated outpatient dialysis and inpatient beds. An analysis that included 1219 patients attending satellite dialysis clinics found that older age was a risk factor for infection. COVID-19 infection was substantially more likely to occur among patients on in-center dialysis compared with those dialyzing at home. 

A study from the Bronx in NY also showed poor outcomes for hospitalized ESKD patients. Elevated inflammatory markers were associated with in hospital death.

Another UK study also found a high prevalence of seropositivity in the outpatient dialysis units. 

Alberici et al.describe their clinical experience with MHD patients cared for at 4 outpatient dialysis facilities that are part of the Brescia Renal COVID Task Force. In a period of 1 month, viral positivity was detected in 94 of their 643 ESRD HD patients (15%). Important findings in the study were the mild form of symptomatology at presentation, the high rate of overall mortality (29%), and emergence of usual risk factors for mortality and acute respiratory distress syndrome in SARS-CoV-2–positive HD patients. In addition, although certain patients were deemed more stable and were managed in the outpatient facility, 3 of those subsequently died, and a substantial portion had significant worsening of their symptoms.

Goicoechea et al. describe the clinical course and outcomes of 36 patients from 2 dialysis facilities caring for 282 patients that were admitted to a tertiary hospital in Madrid based on positive reverse transcription polymerase chain reaction for SARS-CoV-2. They report a mortality rate of 30.5%, and 33% of their patients required mechanical ventilation. 


At our health system of over 23 hospitals in NY, we decided to compare the outcomes of ESKD patients to non ESKD patients. The data was from 13 hospitals and our final cohort had 419 (4%) with ESKD and 10,063 (96%) without ESKD.This is the largest study to date.

What did we find:( similar tweetorial by first author Jia Ng)


1. Patients with ESKD were older, had a greater percentage self-identified as Black, and more comorbid conditions.

2. Patients with ESKD had a higher rate of in-hospital death than those without (31.7% vs 25.4%), odds ratio 1.38, 95% confidence interval 1.12 - 1.70). This increase rate remained after adjusting for demographic and comorbid conditions (adjusted odds ratio 1.37, 1.09 - 1.73).

3. Patients with ESKD had similar rates of mechanical ventilation as those without ESKD (89 [21.2%] vs 2076 [20.6%]). There was no difference in the odds of mechanical ventilation between the groups.

4. The odds of length of stay of seven or more days was higher in the group with compared to the group without ESKD in both the crude (1.62, 95%CI 1.27 - 2.06) and in the adjusted analysis (1.57, 95% 1.22 - 2.02)

5. We conducted stratified analyses to investigate the risk factors of death in the subgroups of ESKD and the non-ESKD separately, with the hypothesis that the risk factors of death and the magnitude of risk factors would differ between the two groups.

6. For patients without ESKD, the independent risk factors for in-hospital death increased age, male sex, cardiovascular disease, cancer, requiring ventilation, requiring vasoactive meds, high blood urea nitrogen, low albumin, high CRP and high ferritin.

7. The diagnosis of hypertension and use of an ACE inhibitor or ARB were associated with a lower risk of in-hospital death in the non-ESKD group.

8. Among patients with ESKD, independent risk factors for in-hospital death were increased age, requiring ventilation and lymphopenia, elevated BUN and high serum ferritin. Black race was associated with a significantly lower risk of death among patients with ESKD.

9. The protective effect of HTN in the non-EKSD group, and the protective effect of Black race in the ESKD group defy easy explanation. Perhaps APOL1 has some protective cardiac effect?

10. This is a large cohort of hospitalized patients with #COVID-19 comparing ESKD and non-ESKD in a diverse patient population. We had prespecified operational definitions for exposures, covariates and outcomes, as well as rigorous adjudication by two independent reviewers for ESKD exposure.

11. What limitations do we have?--Despite the larger size of this study compared to other reports, the ESKD sample may still have been relatively underpowered to find other statistically significant risk factors in mortality. Also there was inability to adjust for remdesivir and dexamethasone. As the evidence of these 2 drugs came after the surge of #COVID-19 cases in our health system, only a small proportion of patients received these drugs.

12. We had 11 PD patients in our admitted cohort. This was also published in a special report as well. Of 419 hospitalized patients with ESKD, 11 were on chronic PD therapy (2.6%). Among those 11, 3 patients required mechanical ventilation, 2 of whom died. Of the entire cohort, 9 of the 11 patients (82%) were discharged alive. While fever was a common presentation, more than half of our patients also presented with diarrhea. Interestingly, 3 patients were diagnosed with culture-negative peritonitis during their hospitalization. Seven patients reported positive SARS-CoV-2 exposure from a member of their household.

In conclusion, among patients hospitalized with COVID-19, those with ESKD had a higher rate of in-hospital death compared to those without ESKD. 

Two recent studies also show the outpatient HD infection and admission rates. A study published in AJKD from Canada showed from universal screening, 4.6% were infected. 


Another French study in KI showed a low incidence of infection of 3.3% in a large >40,000 dialysis patients. Older age, low albumin, and cardiac disease were risk factors for mortality. 


Taken together, the results suggest both a need for further research and the continued need for careful infection control procedures in the ESKD population at risk for #COVID-19.

Wednesday, August 5, 2020

Sunday, August 2, 2020

Topic Discussion: Pyelonephritis but no Urinary Tract Infection?

Pyelonephritis is defined as neutrophilic infiltration within the interstitium suggestive of a bacterial cause of urinary tract infection that might have migrated to the kidney. It rarely evolves into an abscess.

Can this exist without any signs of an urinary track infection? 
A study published in NDT looked prospectively of over 200 cases of acute pyelonephritis. 
What did they find?

Urinary culture was only positive in 31% of patients and blood cultures in 21%
92% did have CT findings of pyelonephritis. 
No differences were noted in patients with positive or negative CT findings in terms of fevers, and wbc counts, pyuria, urine cultures and symptoms. 

Why the negative urinalysis and urine culture? 

The low frequency of positive urine culture may be explained by previous antibiotic treatment, either self-prescribed or prescribed by the general practitioner, and by the possibility that infection was confined to the renal parenchyma. Could reflux disease explain some findings?While the association between acute pyelonephritis  and reflux has been extensively studied in children, the literature does not indicate when reflux must be searched in adults. The authors performed retrograde urethrocystography in the case of recurrent acute pyelonephritis or in the presence of urinary cavities dilation or urinary tract abnormalities: they found reflux in 20.9% of patients. 

In other words, the absence of infected urine does not rule out the diagnosis of acute pyelonephritis in common clinical practice. Renal abscesses are frequent and need to be looked for. Hence, it seems advisable to systematically perform CT or MRI, which have greater sensitivity than ultrasound in detecting them.

Sunday, July 19, 2020

Topic Discussion: COVID and Kidneys- the biopsy experience

As we expand our understanding of COVID-19 related AKI, in the last few weeks, more studies are emerging on what might be the main kidney biopsy findings with COVID related AKI.
We have now established the incidence being around 30-40% in the US.

What is exactly going on in the kidney? Is the virus attacking the kidney or is the renal disease a consequence of "being sick" and or  "inflammatory state".

This figure from an article in JASN summarizes the potential way the SARS-Cov2 might be effecting the kidney



Two recent biopsy series from Columbia and Northwell Nephrology showed the variety of pathology reported in COVID-19



In addition, an autopsy series (specific) to the kidneys showed ATN only.  Finally, in KI, a series of anti GBM were reported in UK related to COVID-19

All recent papers added interesting few things to the ongoing literature.

1. ATN is by far the most common presentation for AKI( if not pre renal)- even in transplanted kidney. Pigment nephropathy from myoglobin or hemoglobin is rare. Vitamin C overdose induced oxalate nephropathy is rare.
2. Podocytopathies( MCD and cGN) are the most common glomerular findings
3. Other glomerular diseases are a varied amount( TMA, ANCA, Membranous GN, anti GBM)
4. The virus was not found in the kidney with immunohistochemistry in all 3 studies.

Does the kidney get infected?- time will tell.. data is mixed



Sunday, June 21, 2020

10 Years of Nephrology Social Media

10 years and a few months ago, I wrote the first nephronpower post. It was simple and about a historical event in nephrology. My inspiration was the Late Nate Hellman from Renal Fellow Network. What has transpired since then is truly amazing for the field of Nephrology.

Few of us started blogging at National conferences, some of us tweeting like a storm. Finally, the academic community noticed this and soon ASN, NKF and all wanted tweets and blogs of their events. The first landmark paper summarizing some of this was in AJKD in 2011.

Following that, was the birth of AJKDblog or then called eAJKD. This allowed for more collaboration and more social media to flourish in nephrology and leading to the ultimate- Nephmadness ( mastermind game by the Topf Sparks team) in 2013.

After 2013, nothing was stopping nephrology to take the lead in social media.
From NephJC to tweetorials to whatsApp to creation of NSMC-- happening so fast and furious!

Nephrologists quickly stormed the social media world to lead and show how it's done!
In NDT is a brief tutorial for how to be social media savvy.

Academic journals- AJKDBlog
Journal club- NephJC
Well ironed blogs- Renal Fellow Network
Online Successfully run interactive game for over 7 years- Nephmadness
Online academy of educators for future social media wannabees- NSMC
Every fellowship program trying to have a twitter account and social media presence.

What else can you ask for?
All this is summarized in recent issue in Seminars in Nephrology by guest editor Joel Topf and includes all various aspects of the social media
Here is a nice tweetorial by Chan on the entire issue

Introduction to social media
Tweet or not to tweet
Twitter based journal clubs
Tweetorials
Podcasting
Newsletters
Visual abstracts
Slack
Semi-private Apps ( WhatsApp)
FOAM quality 
NSMC

Congratulation to the nephrology community to being leaders in education via social media in medicine!

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