Dr. Khalid is a health researcher and science writer with a Ph.D. in clinical research.
What is Chronic Kidney Disease (CKD)?
The non-communicable CKD based on prolonged kidney dysfunction is categorized under multiple kidney function stages (Fraser, 2016). The functional status of the kidney is determined through the glomerular filtration rate (GFR). The conditions including metabolic diseases, anemia, hypertension, and cardiovascular disease potentially elevate the risk of GFR reduction and kidney dysfunction. The kidney function assessment warrants regular investigation of estimated glomerular filtration rate (eGFR) based on serum creatinine. The nephron loss in kidneys under the impact of chronic/acute disease insults potentially elevates the burden of the healthy nephrons that are forced to undergo adaptive hyperfiltration. This episode, if sustained for a longer duration, leads to irreversible glomerular deterioration. Eventually, the progressive loss of kidney function and proteinuria elevate clinical complications to an unprecedented level. The clinicians advocate the need for early identification of CKD in the context of reducing the risk of acute kidney injury (AKI) and its clinical complications. The functional assessment of the kidney is based on the following standard parameters configured by KDIGO (Kidney Disease Improving Global Outcomes). The standard unit of GFR is ml/min/1.73meter square in the context of the following parameters (Fraser, 2016).
- The normal stage of kidney function (G1) is determined by the GFR of greater than 90.
- The mildly reduced stage of kidney function (G2) is indicated by the GFR within the range of 60-89.
- The mildly/moderately reduced stage of kidney function (G3a) is revealed by a GFR of 45-59.
- The moderately to severely reduced stage of kidney function (G3b) is affirmed by a GFR of 30-44.
- The severely reduced stage of kidney function (G5) is testified by a GFR of 15-29.
- The kidney failure (G5) stage is revealed by a GFR of less than 15.
- The persistent albuminuria (A1) category of kidney function is determined by the albumin level of greater than 30mg/g or less than 3mg/mmol. A1 category reveals mildly elevated or normal urine albumin levels.
- The persistent albuminuria (A2) category reveals a moderately elevated urine albumin level of 30-300 mg/g or 3-30mg/mmol.
- The persistent albuminuria (A3) category testifies a severely elevated urine albumin level of greater than 300 mg/g or 30mg/mmol.
- The individuals at a reduced risk of kidney dysfunction do not exhibit albuminuria or sometimes exhibit a little albuminuria and a mildly reduced or normal eGFR (i.e. A1 and/or G2 or G1).
- Individuals with a moderate albuminuria and eGFR of greater than 60 ml/min/1.73meter square experience an elevated risk of kidney dysfunction.
- The measurement of albuminuria is based on ACR (urinary albumin/creatinine ratio)
- Both albuminuria and eGFR independently determine a range of non-renal and renal outcomes based on AKI, cardiovascular disease, and end-stage renal disease (ESRD).
CKD affirmation is based on the following standard parameters (Fraser, 2016).
- A marked reduction in GFR below 60ml per minute per 1.73 square meters in the absence of other renal deterioration for greater than three months.
- Presence of proteinuria, which is a kidney damage marker.
- The functional and structural deterioration of kidney for greater than three months with or without glomerular filtration rate reduction, with associated pathological abnormalities and kidney damage markers (affirmed through imaging tests and urine/blood findings).
What are the Diagnostic Parameters for CKD?
The physicians require investigating the following attributes to affirm the diagnosis of CKD (Fraser, 2016).
- Previous clinical history of renal transplantation
- Histological abnormalities
- Tubular disorders and related abnormalities
- Electrolyte imbalance
- Abnormalities of urine sediment based on renal tubular epithelial cells, granular casts, oval fat bodies, white/red blood cell casts, and hematuria
- Structural abnormalities of kidney, determined through imaging studies
- ACR (urinary albumin-to-creatinine ratio) of greater than 3 mg/mmol or 30 mg/g, characterized by albuminuria
- eGFR reduction below 60 millilitre per minute per 1.73meter square
The individuals affected with one or more the following disease conditions must undertake CKD testing at regular intervals (Fraser, 2016).
- Opportunistic hematuria
- Hereditary kidney disease
- Family history of ESRD
- Systemic lupus erythematosus
- Multisystem disorders
- Cardiovascular disease, including PVD, CHF, and IHD
- Cerebral vascular disease
- Acute kidney injury
What are the Causes of CKD?
The following diseases trigger the development of CKD and its clinical complications (Vaidya & Aeddula, 2020).
- Sickle cell nephropathy
- Plasma cell dyscrasias
- Secondary vasculitis or glomerulonephritis
- Cystic/hereditary diseases
- Chronic tubulointerstitial nephritis
- Primary glomerulonephritis
- Type 1 diabetes mellitus
- Type 2 diabetes mellitus
- Prerenal disease
- Intrinsic renal vascular disease
- Intrinsic glomerular disease
- Intrinsic tubular disease
- Obstructive nephropathy
What are the Symptoms of CKD?
Most of the CKD symptoms and signs appear during its late stages. Some of them are mentioned below (Vaidya & Aeddula, 2020).
- Hypertensive fundal alterations
- Elevated BUN/Uremic frost
- Uremic pericarditis/pericardial friction
- Pigmented skin
- Uncontrolled or malignant hypertension
- Fluid overload, pulmonary edema, and associated shortness of breath
- Uremic pericarditis and associated chest pain
- Ankle/feet swelling
- Muscle cramps and twitches
- Cognitive decline
- Sleep disturbance
- Loss of appetite
What is the Pathophysiology of CKD?
CKD potentially impacts the re-differentiation capacity of the renal tubules (Mullins, Conway, Menzies, Denby, & Mullins, 2016). The renal erythropoietin deficiency due to defective kidney function triggers the development of anemia in chronic kidney disease patients. Furthermore, the deficiency of folate and vitamin B12 in CKD patients elevates their resistance against erythropoiesis-stimulating agents (ASN, 2011). The hepcidin production under the impact of inflammation in CKD patients challenges the absorption of their gut iron while obstructing its passage to erythron. The prerenal azotemia in in CKD patients potentially disrupts the renal vascular supply that triggers the development of AKI. This episode occurs after a marked decrease in circulatory volume or extracellular fluid volume under the impact of sepsis, heart failure, or advanced cirrhosis. The gross failure of renal adaptive mechanisms leads to an elevation in creatinine and BUN levels along with a reduction in glomerular filtration rate (Bindroo & Challa, 2020). Furthermore, the development of renal azotemia or intrinsic renal parenchymal disease adversely impacts the physiological function of tubulointerstitium, vasculature, and glomeruli. Postrenal azotemia, however, manifests through the development of urine outflow obstruction.
Hyperphosphatemia manifests in CKD patients during the stages 4 and 5 under the sustained influence of renal injury (Hruska, Seifert, & Sugatani, 2015). This is because the impaired tubular absorption due to non-functional nephrons impacts the excretion of phosphate. The advanced stages of chronic kidney disease also associate with PTH dysfunction that deteriorates the overall phosphate homeostasis. Furthermore, the skeletal function inhibition in CKD patients also leads to their vascular calcification and hyperphosphatemia. The osteoblastic transition induction under the impact of hyperphosphatemia elevates the calcium-phosphorous product that eventually leads to extraskeletal mineralization. Hyperphosphatemia also triggers calcitriol deficiency while deteriorating the activity of 1-alpha-hydroxylase.
The functional retardation of kidney reciprocates with the development of proteinuria. The tubointestinal injury exacerbates under the influence of protein overload that potentially deteriorates energy level and lysosomal function (Yamaguchi, Tanaka, & Nangaku, 2015). Furthermore, the induction of fibrogenic/inflammatory mediators occurs under the impact of tubular cell injury or activation. These processes initiate under the direct impact of intratubular complement activation. CKD pathogenesis in many scenarios progresses despite a marked reduction in proteinuria that occurs due to the renoprotective effects of renin-angiotensin-aldosterone inhibitors. CKD progression also associates with the tubulointerstitium’s chronic hypoxia. The reduction in peritubular capillary density in CKD patients elevates hypoxia in a manner to induce tubular cells’ phenotypic changes. These processes eventually lead to the development of apoptosis. The alterations in the tubular cells potentially elevates the activity of inflammatory mediators that potentially increases the development of fibrosis and inflammatory cell filtration. The local oxygenation impairment occurs under the impact of fibrosis; however, sterile inflammation develops under the influence of hypoxia. The inflammatory transcription factors induce hypoxic responses in the CKD patients. The oxidative stress and inflammation of the CKD patients develops under the influence of hypoxia that potentially contributes to chronic kidney disease pathogenesis.
CKD manifests through antioxidant capacity impairment as well as the increased accumulation of ROS (reactive oxygen species) (Yamaguchi, Tanaka, & Nangaku, 2015). The oxidative stress in CKD patients also develops under the influence of intra-renal angiotensin system activity, hyperglycemia, uremic toxin, and proteinuria. The Kelch-like ECH-associated protein 1-nuclear factor-erythroid-2-related factor 2 (Keap1-Nrf2) activity impairment dysregulates the cytoprotective responses against exogenous and endogenous stresses in the CKD patients. These pathophysiological processes elevate the inflammation while deteriorating the overall antioxidant defense system of the CKD patients. The deteriorated expression of megalin in CKD patients reduces their proximal tubules’ albumin reabsorption rate that eventually triggers albuminuria and its clinical manifestations. These outcomes substantiate the requirement of managing oxidative stress in CKD patients.
How Can You Manage CKD Through Evidence-Based Interventions?
The following conservative pharmacotherapeutic option(s) could assist the clinical management of CKD and its potential complications (Breyer & Susztak, 2016) (Grill & Brimble, 2018) (Bland, 2016).
- The pharmacotherapy based on ARBs (angiotensin-receptor blockers) and ACE (angiotensin-converting enzyme) inhibitors helps to manage diabetic nephropathy and its clinical complications.
- ARBs and ACE inhibitors potentially reduce albuminuria/proteinuria, thereby decreasing the requirement of renal dialysis.
- The reno-protective effect of ARBs/ACE inhibitors assists in optimizing the diabetic kidney patients’ glomerular hyperfiltration.
- The initial phase of ARBs/ACE inhibitor pharmacotherapy leads to an acute reduction in eGFR (estimated glomerular filtration rate) that helps in controlling a prolonged kidney function loss.
- The ARBs/ACE inhibitor pharmacotherapy efficiently manages diabetic nephropathy while minimizing the renal function loss; however, it fails to challenge the progression of end-stage-renal disease.
- The ARBs or ACE inhibitor pharmacotherapy challenges the renin-angiotensin system; however, the combination of both of these therapies fails to achieve the therapeutic goals.
- The combination treatment of ARBs and ACE inhibitor pharmacotherapies lead to the onset of acute kidney injury, hypotension, and hyperkalemia.
- The treatment of diabetic nephropathy with mineralocorticoid-receptor antagonists including epleronone and spironolactone assists in reducing albimunuria, eGFR, and blood pressure at the cost of hyperkalemia.
- The conservative management strategies must incorporate lifestyle modifications to effectively improve life expectancy and treatment outcomes in CKD patients.
- CKD stage 5 warrants dialysis for managing the eGFR and creatinine level. Each dialysis session is based on a duration of 4 hours. The ESRD patients usually require three dialysis sessions per week based on their clinical parameters.
- Kidney transplantation is another viable option for the enhancing the wellness outcomes of the CKD patients. However, a thorough assessment of transplant intricacies and complications is essentially required while clinically correlating the CKD patients’ reported manifestations and health-related complications.
- Some of the novel therapeutic interventions (under clinical trials) for CKD management are based on the following drugs.
- GS-4997 (ASK1 inhibitor, hypothesized for its anti-inflammatory and protein kinase inhibitor activities)
- VPI-2690B (monoclonal Ab to αVβ3 integrin, hypothesized for inhibiting IGF1 signalling)
- GKT13783 1 (NOX1-4 inhibitor, hypothesized for its antioxidant activity)
- CTP-499 (deuterium containing pentoxyfyl line metabolite, hypothesized for its antifibrotic activity)
- CCX-140 (CCR2 antagonist, hypothesized for its anti-inflammatory activity)
- Baricitinib (JAK1/2 inhibitor hypothesized for its anti-inflammatory activity)
- ASP8232 (vascular adhesion protein 1 inhibitor, hypothesized for its anti-inflammatory activity)
- Finerenone BAY 94-8862 (mineralocorticoid receptor antagonist, hypothesized for its anti-inflammatory and hemodynamic activities)
- Pyridorin (vitamin B6 analog, hypothesized for its antioxidant activity)
- Canaglifloz in (SGLT2 inhibitor, hypothesized for its hemodynamic activity)
- Atrasentan (endothelin receptor A antagonist, hypothesized for its hemodynamic potential
What is the Scope of Using CAM (Complementary and Alternative Medicine) in the Clinical Management of CKD/ESRD?
CAM alone might not provide any remedy to CKD or ESRD. However, the concomitant use of CAM with conservative management approaches could enhance therapeutic outcomes and wellness paradigm of the CKD/ESRD patients (Birdee, Phillips, & Brown, 2013). The CAM approach is based on the administration of mind-body interventions, dietary supplements, and herbs based on the CKD manifestations or clinical symptoms. Deep breathing exercises claim to reduce the oxidative stress in CKD patients. The analysis by Yao and Lin (2019) reveals the renal protective effects of the herbal formulation ‘Eefooton’ in CKD patients. The findings reveal the potential of this drug to delay the dialysis requirement in CKD patients. Eefooton is based on the combination of the following herbs. The clinicians advocate the use of this medicine along with the regular or conservative CKD pharmacotherapy.
- Rhodiola sacra (1.3grams)
- Panax quinquefolius (1.3 grams)
- Ligustrum lucidum (3grams)
- Codonopsis pilosula (3grams)
- Astragalus membranaceus (3grams)
The following herbs also help to protect or enhance kidney function in CKD patients (Prashanth, Baghel, Ravishankar, Gupta , & Mehta, 2010).
- Asphaltum panjabiunum (Shilajit)
- Asparagus racemosus (Shatavari) root
- Tinospora cordifolia (Guduchi) stem
- Saccharum officinalum (Kandekshu) root
- Desmostachya bipinnata (Kusha) root
- Moringa olifera (Shigru) bark
- Crataeva nurvala (Varuna) bark
- Tribulus terrestris (Gokshura) seed
- Boerhavia diffusa (Punarnava) root
- Coriander sativum seeds
- Zingiber officinale or Ginger
What are the Dietary Approaches for CKD Management?
The dietary recommendations assist in improving health-related quality of life of the CKD patients. The following fruits/vegetables require daily consumption by CKD patients to accomplish their nutritional requirements. The patients should avoid using diet salt based on its high potassium content.
- Dietary items with optimum potassium content
- One medium banana
- Melon (one medium slice)
- Half medium avocado
- Half cup coconut water
- Papaya (one medium slice)
- Grapes (one small bunch)
- Jabuticaba (two tea saucer)
- Pineapple (one medium slice)
- One lima type orange
- Ten strawberries
- One medium apple
- Ten acerolas
- Half medium mango
- One medium pear
- One medium peach
- One medium fresh plum
- Lemon juice (half cup)
- Five lettuce leaves
- Half small cucumber
- Watercress (two tea saucers)
- Cabbage (one tea saucer)
- Three medium radishes
- One medium red pepper
- One small tomato
- Half medium carrot
- Raw endive (one tea saucer)
- Raw chard (one tea saucer)
- Raw cabbage (two tea saucers)
- Raw beets (Three tablespoons)
- Chips (One tea saucer)
- Tomato paste (two tablespoons)
- Fennel (one tea saucer)
- Vegetable soups
- Fried vegetables based on cassava, potato, cabbage, and kale
- Potato chips
- Fruit jam
- Concentrated natural fruit juices
- Brown sugar
- Chocolate-based items, including cakes and biscuits
- Concentrated tomato sauce
- Brazil nuts
- Powdered milk
- Espresso coffee
ASN. (2011). Chronic Kidney Disease. California: Henry Ford Health System. Retrieved from https://www.asn-online.org/education/training/fellows/HFHS_CKD_V6.pdf
Bindroo, S., & Challa, H. J. (2020). Renal Failure. In StatPearls. Treasure Island (Florida): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK519012/
Birdee, G. S., Phillips , R. S., & Brown, R. S. (2013). Use of Complementary and Alternative Medicine among Patients with End-Stage Renal Disease. Evidence-Based Completementary and Alternative Medicine. doi:10.1155/2013/654109
Bland , J. (2016). Kidney disease: Personalized lifestyle health care makes a big difference. Integrative Medicine: A Clinician's Journal, 15(6), 14-16. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312831/
Breyer, M. D., & Susztak, K. (2016). Developing Treatments for Chronic Kidney Disease in the 21st Century. Seminars in Nephrology, 36(6), 436-447. doi:10.1016/j.semnephrol.2016.08.001
Fraser, S. D. (2016). Chronic kidney disease: identification and management in primary care. Pragmatic and Observational Research, 21-32. doi:10.2147/POR.S97310
Grill, A. K., & Brimble, S. (2018). Approach to the detection and management of chronic kidney disease. Can Fam Physician, 728-735. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6184972/
Hruska, K. A., Seifert, M., & Sugatani, T. (2015). Pathophysiology of the Chronic Kidney Disease – Mineral Bone Disorder (CKD-MBD). Current Opinion in Nephrology and Hypertension, 24(4), 303-309. doi:10.1097/MNH.0000000000000132
Mullins, L. J., Conway, B. R., Menzies, R. I., Denby, L., & Mullins, J. J. (2016). Renal disease pathophysiology and treatment: contributions from the rat. Disease Models and Mechanisms, 9(12), 1419-1433. doi:10.1242/dmm.027276
Prashanth, G. S., Baghel, M. S., Ravishankar, B., Gupta, S. N., & Mehta, M. P. (2010). A clinical comparative study of the management of chronic renal failure with Punarnavadi compound. Ayu, 31(2), 185-192. doi:10.4103/0974-8520.72388
Vaidya, S. R., & Aeddula, N. R. (2020). Chronic Renal Failure. Treasure Island (Florida): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK535404/#_article-28357_s8_
Yamaguchi, J., Tanaka, T., & Nangaku, M. (2015). Recent advances in understanding of chronic kidney disease. F1000Research, 1-9. doi:10.12688/f1000research.6970.1
Yao, C. A., & Lin, C. H. (2019). Treatment with the herbal formulation Eefooton slows the progression of chronic kidney disease. Medicine, 98(43). doi:10.1097/MD.0000000000017573
This content is for informational purposes only and does not substitute for formal and individualized diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed medical professional. Do not stop or alter your current course of treatment. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.
© 2020 Dr Khalid Rahman
Dr Khalid Rahman (author) from India on April 25, 2020:
Umesh Chandra Bhatt from Kharghar, Navi Mumbai, India on April 24, 2020:
Excellent. Valuable resource. Nice article.