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\def\citeauthor{~C.~Madhavi~Latha,
              ~CH.~Varshitha,
              ~P.~Hari~babu,
              ~SK.~Harshiya,
              ~L.~Charunya,
              ~Sreenivasulu~M}
\def\citetitle{\textbf{Review article on chronic kidney disease}}
\def\copyrightstmt{This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial- ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.}
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\def\RunningAuthor{C. Madhavi Latha et al.}
\firstPage{146}
\articleType{Review Article}
\receivedDate{28 Mar 2022}
\acceptedDate{10 Apr 2022}
\revisedDate{07 Apr 2022}
\journalVolume{2}
\journalIssue{4}
\copyrightYear{2022}
\eISSN{2583-0953}
\journalDoi{10.26452/ijcpms.v2i4.470}
\def\authorCount{6}
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\def\journalTitle{International Journal of Clinical Pharmacokinetics and Medical Sciences}

\title{\textbf{Review article on chronic kidney disease}}
\author{C.~Madhavi~Latha\textsuperscript{*}\textsuperscript{1},  
            CH.~Varshitha\textsuperscript{2}\textsuperscript{\href{https://orcid.org/0009-0001-7594-0289}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            P.~Hari~babu\textsuperscript{2}\textsuperscript{\href{https://orcid.org/0009-0003-2512-5715}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            SK.~Harshiya\textsuperscript{2}\textsuperscript{\href{https://orcid.org/0009-0008-8620-5360}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            L.~Charunya\textsuperscript{2}\textsuperscript{\href{https://orcid.org/0009-0001-7594-0289}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}}, 
            Sreenivasulu~M\textsuperscript{3}~\\[5pt]{\textsuperscript{1}Department of Pharmacology, Ratnam Institute of Pharmacy, Pidathapolur Village and Post, Muthukur (M), SPSR Nellore District, Pidathapolur, Nellore, Andhra Pradesh 524346}~\\{\textsuperscript{2}Ratnam Institute of Pharmacy, Pidathapolur Village and Post, Muthukur (M), SPSR District, Pidathapolur, Nellore, Andhra Pradesh 524346}~\\{\textsuperscript{3}Department of Pharmaceutical Chemistry, Ratnam Institute of Pharmacy, Pidathapolur Village and Post, Muthukur (M), SPSR Nellore District, Pidathapolur, Nellore, Andhra Pradesh 524346}}

\begin{abstract}
The hallmarks of chronic kidney/renal disease (CKD) include patient urogenital abnormalities, anatomical abnormalities, or lowered excretory renal function that may indicate the absence of functioning nephrons. The majority of CKD cases have increased mortality and cardiovascular complaint threat. The difficulty in carrying out renal replacement therapy for those with end-stage renal complaints is an issue far and wide around the globe. Low nephron count at birth, nephron loss with aging, and acute or chronic kidney damage brought on by toxic exposures or illnesses are risk factors for the development and progression of CKD (for illustration, obesity, and type 2 diabetes mellitus). Cases with CKD are managed with an emphasis on early discovery or prevention, treatment of the underlying cause to decelerate development, and attention to secondary processes that fuel continued nephron loss. The pillars of remedy include lowering blood pressure, blocking the renin-angiotensin system, and accepting actions adapted to a case's particular condition. Diagnosis and therapy are necessary for CKD consequences such as secondary hyperparathyroidism, metabolic acidosis, and anemia, which impact cardiovascular health and quality of life.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}CKD,\newline GFR,\newline ESRD,\newline Dialysis,\newline treatment
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright{\Large$^\ast$}Corresponding Author\par Name:\ C.~Madhavi~Latha~\\ Phone:\ +91 90529 87936~\\  Email:\ madhavilathacology@gmail.com
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\section{Introduction}
WHO DEFINES CKD as kidney damage or glomerular filtration rate [GFR] less than 60 ml/min or 1.73 m2 for three months or more, regardless of the underlying cause. Albuminuria, indicated by an albumin-to-creatinine ratio of more than 30 mg/gm in two of three spot urine samples, is a reliable indicator of kidney impairment in many renal disorders. According to the CDC, kidney disease (CKD) is a disorder in which the kidneys are damaged and unable to filter blood wastes as effectively as healthy kidneys. As a result, blood waste builds up in the body, leading to various health issues. More than or equal to three months' worth of structural or functional problems in the kidneys, as shown by kidney damage with or without a reduced GFR\unskip~\cite{1885752:27797269}.

GFR less than 60 mg/min/1.73 m\ensuremath{^{2}} whether or not renal impairment is present. 


\bgroup
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\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/62e84acb-4f9a-46eb-8b5f-e18048c4f0a2-uimage.png}{\includegraphics{images/62e84acb-4f9a-46eb-8b5f-e18048c4f0a2-uimage.png}}{\includegraphics{62e84acb-4f9a-46eb-8b5f-e18048c4f0a2-uimage.png}}
\makeatother 
\caption{\boldmath {The distinction between healthy kidneys and kidneys with diseases}}
\label{f-b4e1c7de134d}
\end{figure}
\egroup
\textbf{Stages of CKD\unskip~\cite{1885752:27797268}}

Stage 1: GFR {\textgreater} 90 ml/min/1.73 m\ensuremath{^{2}} (NORMAL)

Stage 2: GFR 60-89 ml/min/1.73 m2 [MILD]

Stage 3: GFR 30-59 ml/min/1.73 m2 [MODERATE]

Stage 4: GFR 15-29 ml/min/1.73 m2 [SEVERE]

Stage 5: GFR less than 15 ml per minute per square meter [KIDNEY FAILURE].

\textbf{Albuminuria staging:}

\textbf{Stages include:}

Stage 1 (urine ACR 30mg/gm),

Stage 2 (urine ACR 30-300mg/gm), and

Stage 3 (urine ACR {\textgreater} 300mg/gm).

\textbf{Incidence of CKD in India\unskip~\cite{1885752:27797267}}

According to nephrology dialysis transplantation, roughly 7.85 million people in India suffer from chronic renal failure.\textbf{\space }The spectrum's aetiologies included diabetes (41\%), hypertension (22\%), chronic glomerular nephritis (16\%), chronic interstitial disease (5.4\%), ischemic nephropathy (2.7\%), obstructive uropathy (2.7\%), and other causes (5.4\%).\textbf{\space }CKD is thought to affect women more frequently than males [16\% versus 13\%].\textbf{\space }


\bgroup
\fixFloatSize{images/195a9d27-858b-4f97-b289-a3459659b541-uimage.png}
\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/195a9d27-858b-4f97-b289-a3459659b541-uimage.png}{\includegraphics{images/195a9d27-858b-4f97-b289-a3459659b541-uimage.png}}{\includegraphics{195a9d27-858b-4f97-b289-a3459659b541-uimage.png}}
\makeatother 
\caption{\boldmath {CKD prevalence across screening facilities}}
\label{f-90d9b9e01aa5}
\end{figure*}
\egroup

\bgroup
\fixFloatSize{images/a05ff9fe-dc2d-4371-a54a-1e1fba3e4547-uimage.png}
\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/a05ff9fe-dc2d-4371-a54a-1e1fba3e4547-uimage.png}{\includegraphics{images/a05ff9fe-dc2d-4371-a54a-1e1fba3e4547-uimage.png}}{\includegraphics{a05ff9fe-dc2d-4371-a54a-1e1fba3e4547-uimage.png}}
\makeatother 
\caption{\boldmath {Prevalenceof traits connected to and unrelated to CKD in our group}}
\label{f-aa964dc99b39}
\end{figure*}
\egroup

\bgroup
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\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/3e15a7c9-60cc-4943-ab90-dd1a0224e130-uimage.png}{\includegraphics{images/3e15a7c9-60cc-4943-ab90-dd1a0224e130-uimage.png}}{\includegraphics{3e15a7c9-60cc-4943-ab90-dd1a0224e130-uimage.png}}
\makeatother 
\caption{\boldmath {Stage-specific prevalence of CKD in men and women}}
\label{f-ff27b6b79d12}
\end{figure*}
\egroup

\bgroup
\fixFloatSize{images/19d3ce3e-aa4c-4ae9-8609-87f3bd576dc2-uimage.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/19d3ce3e-aa4c-4ae9-8609-87f3bd576dc2-uimage.png}{\includegraphics{images/19d3ce3e-aa4c-4ae9-8609-87f3bd576dc2-uimage.png}}{\includegraphics{19d3ce3e-aa4c-4ae9-8609-87f3bd576dc2-uimage.png}}
\makeatother 
\caption{\boldmath {CKD is widespread in the world}}
\label{f-b5ba67e4f3ea}
\end{figure}
\egroup
\textbf{Causes of CKD\unskip~\cite{1885752:27797274}}


  
  \begin{enumerate}
  \item \relax Diabetes.
  \item \relax Hypertension.
  \item \relax Impaired urine flow.
  \item \relax Kidney disease (interstitial and glomerular nephritis).
  \item \relax Stenosis of the kidney artery.
  \item \relax Certain poisons include lead, solvents like carbon tetrachloride, and fuels.
  \item \relax A developmental issue in the fetus.
  \item \relax Erythematous systemic lupus.
  \item \relax Yellow fever and malaria
  \item \relax A few drugs [NSAIDs].
  \item \relax Abusing illegal substances like heroin or cocaine.
  \item \relax Injury: a physical or blunt hit to the kidney.
  \item \relax Kidney illness with several cysts.
  \end{enumerate}
  \textbf{Risk Factors of CKD\unskip~\cite{1885752:27797270}}

\textbf{1. Clinical}



\begin{itemize}
  \item \relax Diabetes mellitus.
  \item \relax Obesity;
  \item \relax Hypertension;
  \item \relax Cardiovascular Disease.
  \item \relax  Malignancy.
  \item \relax  Renal stones.
  \item \relax  Obstruction of the urinary tract.
  \item \relax  Decreased kidney mass (low birth weight, nephrectomy).
  \item \relax  Acute renal damage in the past.
  \item \relax  Smoking.
  \item \relax  Using drugs intravenously.
  \item \relax  Kidney illness in the family history.
  \item \relax  Immune system disorders.
\end{itemize}
  \textbf{2. Sociodemographic}



\begin{itemize}
  \item \relax Older than 60 years.
  \item \relax Minority races.
  \item \relax  Low earnings.
  \item \relax Limited education.
\end{itemize}
  \textbf{3. Alleles associated with APOL 1 risk.}



\begin{itemize}
  \item \relax The sickness and trait of sickle cell.
  \item \relax Kidney polycystic disease.
  \item \relax  Alport syndrome is characterized genetically by kidney impairment, hearing loss, and atypical eyes.
  \item \relax  Urinary tract and congenital kidney abnormalities.
  \item \relax  Additional family factors.
\end{itemize}
  
\bgroup
\fixFloatSize{images/54b0ff97-ef00-4aa0-9c6e-7f00d054049b-uimage.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/54b0ff97-ef00-4aa0-9c6e-7f00d054049b-uimage.png}{\includegraphics{images/54b0ff97-ef00-4aa0-9c6e-7f00d054049b-uimage.png}}{\includegraphics{54b0ff97-ef00-4aa0-9c6e-7f00d054049b-uimage.png}}
\makeatother 
\caption{\boldmath {Risk Factors of CKD}}
\label{f-804b648c278c}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/20727cd1-13ac-4b67-b7bc-12cf94113ae2-uimage.png}
\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/20727cd1-13ac-4b67-b7bc-12cf94113ae2-uimage.png}{\includegraphics{images/20727cd1-13ac-4b67-b7bc-12cf94113ae2-uimage.png}}{\includegraphics{20727cd1-13ac-4b67-b7bc-12cf94113ae2-uimage.png}}
\makeatother 
\caption{\boldmath {Signs and symptoms of CKD}}
\label{f-2cd047b6d299}
\end{figure*}
\egroup

\bgroup
\fixFloatSize{images/bf2802fd-713e-44c1-b9eb-245827efb8f6-uimage.png}
\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/bf2802fd-713e-44c1-b9eb-245827efb8f6-uimage.png}{\includegraphics{images/bf2802fd-713e-44c1-b9eb-245827efb8f6-uimage.png}}{\includegraphics{bf2802fd-713e-44c1-b9eb-245827efb8f6-uimage.png}}
\makeatother 
\caption{\boldmath {Pathophysiology of CKD}}
\label{f-fc0cc015fa58}
\end{figure*}
\egroup
\textbf{Complications of CKD\unskip~\cite{1885752:27797275}}



\begin{itemize}
  \item \relax Hyperkalaemia, fluid retention, and cardiovascular disease are among the examples.
  \item \relax Fractures are more likely in those with weak bones
  \item \relax Anaemia.
  \item \relax  Reduced fertility, erectile dysfunction, or decreased sex drive
  \item \relax Your central nervous system is harmed.
  \item \relax A diminished immunological response.
  \item \relax Obstetric problems that put the mother and growing fetus in danger.
  \item \relax  Irreversible kidney disease (ESRD).
\end{itemize}
  \textbf{Diagnostic Studies of CKD\unskip~\cite{1885752:27797272}}


  
  \begin{enumerate}
  \item \relax Urine analysis
  \item \relax Urine culture
  \item \relax Hematocrit test
  \item \relax Renal function test
  \item \relax Angiography.
  \item \relax Formulas for calculating the GFR rate
  \end{enumerate}
  

\begin{itemize}
  \item \relax Dietary changes in the research of renal disease
\end{itemize}
  
  
  \begin{enumerate}
  \item \relax GFR is calculated as follows: 186.3 x (serum creatinine) x age x 0.742 (if female)
  \end{enumerate}
  

\begin{itemize}
  \item \relax Cockcroft-Gault equations.
\end{itemize}
  
  
  \begin{enumerate}
  \item \relax Men - (140-age (years) x (body weight (kg))/ (72)x(serum creatinine (mg/dl)). 
  \item \relax 0.85 times as much for women as men.
  \end{enumerate}
  \textbf{Management of CKD\unskip~\cite{1885752:27797271}}


  
  \begin{enumerate}
  \item \relax Non - Pharmacological Management
  \end{enumerate}
  a. Nutritional therapy: 


  
  \begin{enumerate}
  \item \relax 35kcal/kg/day\textless\ 60yrs, 30-35kcal/kg/day {\textgreater}or= 60 yrs.
  \end{enumerate}
  b. Protein intake: 


  
  \begin{enumerate}
  \item \relax Stage 1-3 -- 0.75gm/kg/day
  \item \relax Stage 4 or 5(not on dialysis) {\textendash} 0.6gm/kg/day.
  \item \relax Stage 5(on dialysis){\textendash} 1.2-1.3gm/kg/day.
  \end{enumerate}
  

\begin{itemize}
  \item \relax All stages (if malnourished){\textendash} eat additional protein.
\end{itemize}
  c. Fluids: 


  
  \begin{enumerate}
  \item \relax Urine output + 1000ml.
  \item \relax Limit IDWG (interdialytic weight gain){\textendash} 2-5\% estimated dry weight.
  \end{enumerate}
  d. Maintain food diet: 



\begin{itemize}
  \item \relax Avoid super-sized beverages. 
  \item \relax Limit salty foods.
  \item \relax Add lemon or lime juice to the Water.
\end{itemize}
  e. Water and electrolyte balance: 

1. Daily fluid consumption equals urine output from the previous day plus 600 ml

2. a rigid input-output chart for fluids.

f. Every day weighing.

g. Refrain from nephrotoxins.

\textbf{2. Pharmacological Management: }

The first goal of treatment is to identify vulnerable people with the chronic renal disease early.



\begin{itemize}
  \item \relax To manage high blood pressure.
  \item \relax To regulate blood sugar levels.
  \item \relax To address other root causes.
  \item \relax To avoid issues and further declines in renal function.
  \item \relax Care for underlying illnesses (Diabetes, HTN, Autoimmune diseases, etc.)
\end{itemize}
  \textbf{Treatment of fluid overload}: Furosemide (oral/IV) 40{\textendash}120 mg daily is a diuretic.

\textbf{Treatment of hypertension}: BP maintenance \textless\ 130/80mmhg, Antihypertensive and cardiovascular agents are used \textbf{\unskip~\cite{1885752:27797276}}.

1. ACE (angiotensin-converting enzyme) inhibitors, such as the oral medications lisinopril (5-40 mg) and ramipril (2-5 mg).

2. ARBs (angiotensin two receptor blockers): An example is losartan (oral) 25{\textendash}100 mg daily.

80{\textendash}160 mg of valsartan (oral) per day

\textbf{Treatment of anemia}


  
  \begin{enumerate}
  \item \relax Injection of erythropoietin{\textendash} 50-100 units IV/SC thrice a week 
  \item \relax Treatment is initiated at HB \textless\ 10gm/dl.
  \item \relax Tab ferrous sulfate -200mg thrice a day.
  \end{enumerate}
  \textbf{Treatment of hyperkalemia or metabolic acidosis}


  
  \begin{enumerate}
  \item \relax 10\% calcium gluconate IV -- 10-20 ml over 2-5mins+.
  \item \relax Sodium bicarbonate IV {\textendash} 8.4\% 50 meq over 5 mins+.
  \item \relax Regular insulin IV{\textendash} 10 units in 50-100ml 50\% glucose.
  \end{enumerate}
  \textbf{Treatment of hyperphosphatemia}


  
  \begin{enumerate}
  \item \relax Phosphate binders
  \end{enumerate}
   Examples: calcium acetate or calcium carbonate {\textendash} 2 capsules (1334mg orally with food).

\textbf{Treatment of hypocalcemia}


  
  \begin{enumerate}
  \item \relax Calcium citrate {\textendash} 1gm per day oral.
  \item \relax Vit D supplement {\textendash} 2 tablets (800IU) once daily.
  \end{enumerate}
  \textbf{Treatment of pruritus}


  
  \begin{enumerate}
  \item \relax Capsaicin cream or cholestyramine.
  \end{enumerate}
  \textbf{Treatment of bleeding}


  
  \begin{enumerate}
  \item \relax Desmopressin{\textendash} 0.3mcg/kg IV over 15-30 mins.
  \end{enumerate}
  \textbf{Other Therapy\unskip~\cite{1885752:27797265}}

\textbf{Dialysis}

When the kidneys cannot perform those functions, dialysis removes fluid and uremic waste products from the body. Those with edema that doesn't respond to therapy, hepatic coma, hyperkalemia, hypercalcemia, hypertension, and uremia may also benefit from its usage. There are two kinds.

\textbf{Haemodialysis}

A medical procedure to remove fluid and waste products from the blood and to correct the electrolyte imbalance. This is accomplished using a machine and a dialyzer called an "ARTIFICIAL KIDNEY." Haemodialysis is used to treat both acute and chronic kidney failure. 

\textbf{Principle of Haemodialysis}

Haemodialysis is based on the concepts of diffusion, osmosis, and ultrafiltration.

\textbf{Types of Haemodialysis\unskip~\cite{1885752:27797273}}

\textbf{1. Conventional hemodialysis:} This procedure is typically performed a week thrice for about three to four hours per treatment. The patient's blood is drawn out through a tube at 200 to 400 ml per minute.

\textbf{2. Daily hemodialysis:} Less stressful but necessitates more frequent access; this kind of dialysis is often utilized by patients who perform their at-home treatments.

\textbf{3. Nocturnal hemodialysis: }it is like conventional hemodialysis except it is performed 3-6 nights a week and between 6 and 10 hrs per session while the patients sleep.

\textbf{Peritoneal Dialysis} \textbf{\space }

The usage of peritoneal dialysis is less when compared to hemodialysis due to the complication (peritonitis, then subsequent septic shock) associated with peritoneal dialysis.  

\textbf{Renal Transplant}

The preferred course of treatment for people with irreversible renal failure. Unfortunately, the availability of organs restricts the utilization of transplantation.
    
\section{\textbf{Conclusion}}
Cases with CKD are managed with an emphasis on early discovery or prevention, treatment of the underlying cause to decelerate development, and attention to secondary processes that fuel continued nephron loss. The pillars of remedy include lowering blood pressure, blocking the renin-angiotensin system, and accepting actions adapted to a case's particular condition. It has been concluded that diagnosis and therapy are necessary for CKD consequences such as secondary hyperparathyroidism, metabolic acidosis, and anemia, which impact cardiovascular health and quality of life.

\textbf{Acknowledgement }

The authors are thankful to the Correspondent \& Principal Dr. M Sreenivasulu from Ratnam Institute of Pharmacy, Pidathapolur Village and Post, Muthukur (M), SPSR Nellore District, Pidathapolur, Nellore, Andhra Pradesh for providing the necessary facilities to carry out this review work.

\textbf{Conflict of Interest} \textbf{\space }

The authors declare no conflict of interest, financial or otherwise. 

\textbf{Funding Support} \textbf{\space }

The authors declare that they have no funding for this study.
    
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