Vitamin D therapy in IgA Nephropathy

While vitamin D has shown to be beneficial in reducing proteinuria in patients with chronic kidney disease (CKD), the role of activated vitamin D replacement in IgA Nephropathy is not well studied.  A recent open-label, nonplacebo-controlled randomized study published in the AJKD looks at this particular question.  The corresponding author Dr Hong Zhang (HZ) from the Peking University Institute of Nephrology in China discusses this article with Dr Jordan Weinstein (eAJKD).

eAJKD: By what mechanisms does activated vitamin D reduce proteinuria?

HZ:  The effect could be mediated by 2 mechanisms. The first is suppression of the renin-angiotensin-system as animal studies have demonstrated that vitamin D directly inhibits renin expression in the kidney. The other effect is through inhibition of the inflammatory and fibrotic NF-kB pathway.  Furthermore, two clinical trials of activated vitamin D or its analogues have shown a decrease in urinary TGF-b, which strongly suggests antifibrotic effect in the kidney.

eAJKD: Do you feel that reduced proteinuria from vitamin D or its analogues is related to common or distinct mechanisms in diabetic nephropathy versus IgA nephropathy?

HZ:  We think that the mechanisms are similar.  The activation of the renin-angiotensin-system and the stimulation of inflammatory and fibrosis processes are common progression pathways in both diabetic and IgA nephropathy. In our trial, calcitriol reduced the proteinuria by 19%, an effect similar to that observed in diabetic nephropathy (18%). A study by Fishbane et al found that vitamin D analogues reduced proteinuria in both diabetic and nondiabetic patients with kidney disease.

eAJKD: The medical literature contains many studies supporting the benefits of vitamin D, yet large prospective randomized control trials (RCT) are either lacking or disappointing. Do you anticipate large vitamin D RCTs will be done in nephrology?

HZ: Activated vitamin D and its analogs are likely reno protective. There have been several small clinical trials that evaluate the effect of these agents on reducing proteinuria. The VITAL study was a trial of 281 patients with type 2 DM that showed that patients who received paricalcitol had a significant reduction in proteinuria at the 24 weeks follow-up. Residual albuminuria in patients with diabetic nephropathy on RAAS inhibition was further lowered by paricalcitol 2 mcg/day.  Based on these reports, we speculate that vitamin D is a promising strategy for reducing albuminuria. However, trials looking at endpoints such as progression to ESRD are lacking. A large-scale randomized controlled trial with long-term follow-up will be important to evaluate the efficacy and safety of vitamin D in managing CKD.

eAJKD: Do you believe that a larger, longer, placebo-controlled version of your study would show benefits with regard to kidney function and progression to ESRD?

HZ: In IgA nephropathy, reduction in proteinuria is a key protective factor for kidney function. Results from observational studies or clinical trials on vitamin D in patients with IgA nephropathy have been associated with antiproteinuria effect. Thus, the protein reduction associated with vitamin D could translate to a reduction in kidney failure events as defined by doubling creatinine or progression to ESRD. However, trials with short follow-up, including our study or the VITAL study, could not demonstrate this benefit. On the contrary, there was a trend towards decreasing eGFR in the calcitriol treated patients. This phenomenon is likely attributed to the disturbance of creatinine metabolism by vitamin D, as we discussed in our paper. Another reason could be the inhibition of the rnnin-angiotensin-system.  We think that it is difficult to draw a conclusion about vitamin D on long-term kidney function from short term follow-up trials.

To view the entire article, visit AJKD.

Comments

  1. Steven Fishbane MD says:

    The list of published studies linking Vitamin D treatment to proteinuria reduction continues to grow. It is clear, however, that a large, well powered study is needed. In many areas of medicine the literature on a subject starts out positive and then turns negative as more, larger and better studies are reported. Nonetheless, the protective effects of Vitamin D are biologically plausible and animal models support the benefit of treatment. One would suspect that that benefical effects of treatment extend beyond the renin-angiotensin system since most patients are already treated with RAS blocking drugs.

  2. Kenar jhaveri says:

    Does the same effect hold if inactivated vitamin d is given ? In other words, ergocalciferol treatment? Any thoughts on that ?

  3. Sarah Hill says:

    Interesting study, I really enjoyed reading this. When you talk about vitamin D, do you mean supplement such as these? Vitamin D3 (3000 IU)

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