Copyright: kojinaka / 123RF Stock Photo

The nephrology trainees in the US (and around most of the developed world) are taught to look at chronic kidney disease (CKD) as the product of the increasing disease burden of diabetes, hypertension, and cardiovascular disease. Yet, how many of us have paused to ponder about the extent and magnitude of infectious etiologies as being a major cause of CKD? And not just hepatitis and HIV, but more common infectious illnesses.

Why We Need to Broaden Our Perspective

Nephrologists must be cognizant of the bi-directional relationship that exists between CKD and infectious diseases, as highlighted in the recent article in AJKD by Jha et al.  While the article focuses on this relationship in the Asia Pacific region, we must appreciate that our practice of medicine needs to keep pace with a world that is increasingly “flat, hot, and crowded” (to quote Thomas Friedman). The past year saw Asia Pacific emerge as the leading source of immigrants to the US. Similarly, we have all witnessed the heart-breaking exodus of humanity from Syria and its war ravaged neighbors to Europe.

Regardless of the trends in human migration, the next global epidemic (think Zika or Ebola) could bring an unexpected sequelae of kidney disease burden, the likes of which we are unprepared. Unlike chronic diseases like diabetes, the incidence/prevalence of infectious diseases can be “pulsatile”. Before things get overwhelming in such a hypothetical (but not unexpected) scenario, it is important for nephrology and infectious disease clinicians to anticipate, exchange data and information, and prepare. Jha et al’s article underlines the need for such an infrastructure.

The Bidirectional Relationship

Now that we have taken our blinders off, let’s summarize Jha et al’s review. Infections contribute to the development and progression of CKD, and kidney involvement is common in malaria, leptospirosis, TB, HIV, hepatitis B and C, and fungal infections, to identify a few. While the initial presentation is often that of AKI, chronic GN and chronic interstitial nephritis, both from infections and treatments, are dominant pathologic manifestations in regions like China and South Asia.

While North America and Europe battle non-communicable diseases, up to 60% of deaths and disability-adjusted life-years in parts of Asia Pacific are attributable to infections.  Kidney involvement is an independent and major contributor to mortality and morbidity in these infections, with mortality rate of infection associated with AKI approaching 52%. A significant number of patients go on the develop CKD, even when cured of the initial infection.  This might be related to the varying pathogenetic possibilities that cause CKD in the setting of infections: direct invasion, immune mechanisms, multi-organ failure, hepatorenal syndrome, hemolysis, and nephrotoxicity from antimicrobial therapies.

These are staggering numbers. However, pre-existing CKD in itself is a risk for infections. As might be expected, the authors point out the increased risk of HBV and HCV in advanced CKD patients owing to frequent transfusions. The risk of TB is especially high, 10-15 times the rate seen in the general population in CKD patients, and more than 50 times higher in patients receiving kidney replacement therapy (dialysis or transplantation).

Conclusion

The call from Jha et al’s timely review forces us to move past the paradigm of CKD as a non-communicable disease. A number of infectious diseases (beyond HIV, HBV, and HCV) discussed in this review occur right here in the US. TB should not surprise anyone. Leptospirosis continues to be reported with alarming regularity nationwide (California, Colorado, Florida). And while malaria might have been eliminated from the US, recent migrants and international travelers from endemic countries could still carry the infection.  Hence, Jha et al’s review helps shed light on the under-recognized but global causes of CKD.

Dr. Veeraish “VC” Chauhan
AJKD Blog Contributor 

To view the article full-text or PDF (freely available), please visit AJKD.org.